Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 3-day-old female Pinto was admitted with profuse watery diarrhea and severe hypovolemic shock. After 1 week of intensive care, the foal developed seizures associated with profound serum electrolyte abnormalities suggestive of hypoadrenocorticism. Treatment with prednisone and isotonic saline (0.9% NaCl) solution led to prompt clinical response. Premature withdrawal of prednisone resulted in relapse of clinical signs. A diagnosis of adrenal insufficiency was made on the basis of clinical signs, electrolyte abnormalities, low baseline cortisol concentration, and lack of response to administration of exogenous adrenocorticotropin. Two months later, adrenocortical function was normal and the foal was doing well clinically. Clinical signs of acute adrenal insufficiency in neonatal foals can be confused with other conditions, such as septicemia, enteritis, and ruptured urinary bladder. A persistently low serum sodium-to-potassium ratio associated with CNS malfunction should warrant investigation of adrenal gland function. Acute hypoadrenocorticism in foals may be reversible.
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PMID:Adrenal insufficiency in a neonatal foal. 960 31

Sequential cleavage of the precursor protein pre-pro-opiomelanocortin (POMC) generates the melanocortin peptides adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) alpha, beta and gamma as well as the opioid-receptor ligand beta-endorphin. While a few cases of isolated ACTH deficiency have been reported (OMIM 201400), an inherited POMC defect has not been described so far. Recent studies in animal models elucidated a central role of alpha-MSH in the regulation of food intake by activation of the brain melanocortin-4-receptor (MC4-R; refs 3-5) and the linkage of human obesity to chromosome 2 in close proximity to the POMC locus, led to the proposal of an association of POMC with human obesity. The dual role of alpha-MSH in regulating food intake and influencing hair pigmentation predicts that the phenotype associated with a defect in POMC function would include obesity, alteration in pigmentation and ACTH deficiency. The observation of these symptoms in two probands prompted us to search for mutations within their POMC genes. Patient 1 was found to be a compound heterozygote for two mutations in exon 3 (G7013T, C7133delta) which interfere with appropriate synthesis of ACTH and alpha-MSH. Patient 2 was homozygous for a mutation in exon 2 (C3804A) which abolishes POMC translation. These findings represent the first examples of a genetic defect within the POMC gene and define a new monogenic endocrine disorder resulting in early-onset obesity, adrenal insufficiency and red hair pigmentation.
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PMID:Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. 962 Jul 71

Many patients with acquired immune deficiency syndrome (AIDS) have symptoms consistent with adrenal insufficiency, but only a small subset of these patients meet criteria for adrenal insufficiency during a short corticotropin (ACTH) stimulation test. We hypothesized that patients with AIDS and symptoms of adrenal insufficiency who produce normal amounts of cortisol in response to administration of 0.25 mg cosyntropin may nevertheless produce lower amounts of cortisol in a course of 24 hours than comparably sick AIDS patients without symptoms of adrenal insufficiency or comparably sick patients without AIDS. We studied four groups of male patients: AIDS patients with symptoms suggestive of adrenal insufficiency but with a normal response to cosyntropin (group I), AIDS patients without symptoms suggestive of adrenal insufficiency (group II), human immunodeficiency virus (HIV)-negative patients with serious acute or chronic illness (group III), and healthy subjects (group IV). The following variables were examined: age, CD4 cell count, Acute Physiologic and Chronic Health Evaluation (APACHE) score, serum cortisol and plasma ACTH at baseline; serum cortisol at 30 and 60 minutes after intravenous administration of 0.25 mg cosyntropin; and 24-hour urinary free cortisol. The four groups had a similar mean age and baseline plasma ACTH and serum cortisol levels. However, a change in cortisol from baseline to 30 and 60 minutes after administration of cosyntropin was significantly smaller in both groups of AIDS patients than in the sick patients without AIDS and normal subjects. There were also differences noted between the two groups of AIDS patients: both baseline and stimulated levels of cortisol tended to correlate directly with ACTH levels in patients without symptoms of adrenal insufficiency, while this relationship appeared to be inverse in patients with symptoms suggestive of adrenal insufficiency (r = -.57 to -.7, P < .05 to .14). The 24-hour urinary free cortisol levels were similar among all groups, but correlated strongly with baseline and stimulated serum cortisol levels only in patients with AIDS and symptoms of adrenal insufficiency (r = .8 to .9, P < .002 to .015). We conclude that (1) AIDS patients with and without symptoms of adrenal insufficiency may have either normal adrenal function or somewhat suboptimal adrenal reserve as demonstrated by a blunted cortisol response during the short ACTH stimulation test in comparison to HIV-negative comparably sick patients or healthy subjects; and (2) 24-hour urinary free cortisol is not a useful test for detection of subtle abnormalities of adrenal function in patients with AIDS.
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PMID:Twenty-four-hour urinary free cortisol in patients with acquired immunodeficiency syndrome. 962 68

The rapid cosyntropin stimulation test offers a simple means for detecting adrenal insufficiency. In contrast, assessment of suspected hypercortisolism (Cushing's syndrome) is difficult because cortisol levels fluctuate with intermittent release of corticotropin from the pituitary or from tumors. Also, a number of medications affect cortisol levels, leading to false-positive or false-negative results. The classic low-dose followed by high-dose dexamethasone test is cumbersome, and other, simpler studies, such as the overnight high-dose dexamethasone suppression test, may prove more practical and cost-effective. With both high and low levels of adrenal glucocorticoids, awareness and early recognition of the symptoms are important. An endocrinologist should be consulted when the overnight dexamethasone suppression test or the 24-hour urine cortisol collection is abnormal or if clinical suspicion is high despite normal results on screening tests.
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PMID:Assessment of adrenal glucocorticoid function. Which tests are appropriate for screening? 967 62

Pro-opiomelanocortin (POMC) is the precursor of melanocortins (adrenocorticotropin: ACTH, beta-endorphin, beta-lipotropin: beta-LPH, corticotropin like intermediate peptide, alpha-, beta- and gamma-melanocyte-stimulating hormone: alpha-, beta- and gamma-MSH) some of which act in the brain to reduce food intake and are potential mediators of leptin action. Recently, three different mutations in the POMC gene (POMC) were identified in two unrelated children that lead to early-onset extreme obesity, adrenal insufficiency, and red hair pigmentation. In the present study we systematically screened the coding region of POMC in 96 extremely obese children and adolescents, 60 healthy underweight individuals and 46 patients with anorexia nervosa (AN) and identified several variants. a) A 9 and an 18 base pair insertion (9bp and 18bp: AGC AGC GGC and AGC AGC GGC AGC AGC GGC, respectively, between codon 73 and 74; 1,2). These in-frame variants lead to the insertion of three or six amino acids (Ser-Ser-Gly; Ser-Ser-Gly-Ser-Ser-Gly) carboxy-terminal to gamma-MSH. Frequencies of the 9bp insertion allele varied between 3 and 5% among the different study groups (Pearson's chi2 P>0.5). b) Both an out-of-frame 6 bp insertion (within codon 176: GGG CCC) leading to the insertion of two amino acids (Arg-Ala) and a premature stop-codon (G-7316-T: Glu-180-Stop) within the gamma-LPH sequence were maternally inherited in an obese female proband. This proband inherited another missense mutation from her father (Glu-188-Gly). c) A missense mutation (G-7016-A; Asp-80-Asn) was observed in a single patient with AN who also harboured the 9bp insertion on a paternally derived haplotype. d) The allelic co-occurence of two silent mutations (C-6982-T and C-7285-T) was detected in two obese subjects. e) Two further silent mutations (C-3832-T; C-7111-G) were detected in an underweight and an obese subject, respectively. We conclude that the POMC gene harbors several different polymorphisms and mutations, none of which can readily be associated with the phenotypes under study.
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PMID:Systematic mutation screening of the pro-opiomelanocortin gene: identification of several genetic variants including three different insertions, one nonsense and two missense point mutations in probands of different weight extremes. 976 93

A 60-year-old woman was admitted with severe hyponatremia. Basal values of adrenocorticotropic hormone (ACTH), thyroid hormone and cortisol were normal on admission. Impairment of water diuresis was observed by water loading test. Initially, we diagnosed her condition as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). By provocation test, we finally confirmed that the hyponatremia was caused by hypothalamic adrenal insufficiency. The basal values of ACTH and cortisol might not be sufficient to exclude the possibility of adrenal insufficiency. Therefore, it is necessary to evaluate adrenal function by provocation test or to re-evaluate it after recovery from hyponatremia.
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PMID:Severe hyponatremia caused by hypothalamic adrenal insufficiency. 1039 72

A case of chronic primary adrenal insufficiency without hyperpigmentation in a 64-year-old woman is reported. Due to the absence of hyperpigmentation the diagnosis was delayed and she became critically ill. During endocrine evaluation, in order to investigate the mechanism responsible for the absence of hyperpigmentation, skin biopsy was done and hormones responsible for the skin pigmentation were measured. Absence of hyperpigmentation is explained by high degree of melanosome degradation in secondary lysosomes called "compound melanosomes", which overwhelmed increased stimulation of the skin pigmentation. Melanocyte-stimulating hormones were elevated with a strikingly high beta-LPH/ACTH ratio. To our knowledge, this is the first study of pathogenic mechanisms responsible for the absence of hyperpigmentation in white Addison's disease.
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PMID:White Addison's disease: what is the possible cause? 1040 15

Antalarmin is a pyrrolopyrimidine compound that antagonizes corticotropin-releasing hormone (CRH) type 1 receptors (CRHR1). In order to assess the effects of antalarmin treatment on hypothalamic-pituitary-adrenal (HPA) function we measured the plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone in animals treated with either antalarmin or vehicle for 1 week or for 8 weeks. We found that antalarmin treatment for 1 week did not affect basal concentrations of ACTH or corticosterone. In contrast, treatment for 8 weeks significantly lowered basal ACTH and corticosterone concentrations and also significantly decreased the basal corticosterone to ACTH ratio, indicating decreased basal adrenocortical responsiveness to ACTH. However, immobilization stress resulted in ACTH and corticosterone concentrations that were the same in animals treated with vehicle or antalarmin for either 1 or 8 weeks. We conclude that even though 8-week antagonism of CRHR1 by the non-peptide antalarmin blunts basal concentrations of ACTH and corticosterone, and affects the adrenal responsiveness to ACTH, it does not blunt the HPA response to acute stress, and it does not appear to cause stress-induced adrenal insufficiency.
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PMID:Chronic administration of the non-peptide CRH type 1 receptor antagonist antalarmin does not blunt hypothalamic-pituitary-adrenal axis responses to acute immobilization stress. 1042 33

Inherited adrenocorticotropin (ACTH) insensitivity syndromes comprise a group of rare diseases in which resistance to ACTH is either the sole feature or associated with other symptoms. This review focuses on two autosomal recessive disorders, familial glucocorticoid deficiency (FGD) (MIM*202200) and the triple A syndrome (MIM*231550), which have at least three different molecular aetiologies. In FGD, several missense mutations within the coding region of the ACTH receptor (MC2-R) have been identified in some, but not all patients, and segregation analyses and functional studies in a Y6 cell expression system confirmed that these mutations cause the disease. Some cases of FGD are not linked to the MC2-R locus on chromosome 18p11.2 suggesting genetic heterogeneity. The triple A syndrome is clinically characterized by the triad of adrenal insufficiency, achalasia and alacrima and a variety of neurological symptoms. After excluding several candidate genes we mapped this syndrome to a 6 cM interval on chromosome 12q13 with no indication for genetic heterogeneity. The identification of the gene(s) causing FGD without mutations in the MC2-R and causing the triple A syndrome may reveal novel aspects in cell signalling and neuroendocrinology.
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PMID:ACTH resistance syndromes. 1069 92

The hypothalamic-pituitary-adrenal (HPA) axis, including hypothalamic corticotropin-releasing hormone (CRH) and pituitary corticotropin, is one of the first endocrine systems to develop during fetal life, probably because glucocorticoid secretion is necessary for the maturation of many essential fetal organs. Consistent with this, pregnant mice with an inactivating mutation in the Crh gene deliver CRH-deficient offspring that die at birth with dysplastic lungs, which can be prevented by prenatal maternal glucocorticoid treatment. But children lacking the ability to synthesize cortisol (because of various genetic defects in adrenal gland development or steroidogenesis) are not born with respiratory insufficiency or abnormal lung development, suggesting that the transfer of maternal glucocorticoid across the placenta might promote fetal organ maturation in the absence of fetal glucocorticoid production. We used pregnant mice with a normal HPA axis carrying fetuses with CRH deficiency to characterize the relative contributions of the fetal and maternal adrenal to the activity of the fetal HPA axis, and related these findings to fetal lung development. We found that in the presence of fetal adrenal insufficiency, normal fetal lung development is maintained by the transfer of maternal glucocorticoid to the fetus, specifically during the circadian peak in maternal glucocorticoid secretion.
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PMID:Circadian rise in maternal glucocorticoid prevents pulmonary dysplasia in fetal mice with adrenal insufficiency. 1086 Oct


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