Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Individuals with type 1 diabetes mellitus (T1D) at risk for Addison's disease (AD) can be identified with RIAs for autoantibodies to the adrenal antigen 21-hydroxylase (21-OHAA). Screening individuals with T1D for 21OH-AA shows a relatively high prevalence of positive autoantibodies (1.4%, 38 of 2696 subjects). After detection of 21-OHAA, individuals were evaluated with endocrine testing, including baseline cortisol, ACTH, and plasma renin activity and low (1 mug) and high (250 mug) dose cortrosyn stimulation. Typing for DR and DQ alleles and for the major histocompatibility complex class I-related chain A (MICA) gene polymorphisms was performed. Six individuals were diagnosed with AD; five were identified on initial endocrine evaluation. Follow-up over 2.9 yr yielded one additional diagnosis of AD. Endocrine testing showed a correlation between baseline ACTH and peak cortisol (r = -0.61; P < 0.0001), baseline and peak cortisol (r = 0.70; P < 0.0001), and stimulated cortisol after low- and high-dose testing (r = 0.92; P < 0.0001). DR3-DQ2/DR4-DQ8 with DRB1* 0404 was associated with expression of 21-OHAA. At 2 yr, individuals homozygous for MICA5.1 had AD-free survival of 60% compared with 100% AD-free survival in those who were not homozygous for MICA5.1. Homozygosity for MICA5.1 may increase progression to overt AD among 21-OHAA-positive individuals.
 ...
PMID:Endocrine and immunogenetic testing in individuals with type 1 diabetes and 21-hydroxylase autoantibodies: Addison's disease in a high-risk population. 1548 92

Salt appetite was investigated in 14 patients with congenital adrenal hyperplasia of the salt-wasting form (SW group), 12 patients with the simple virilized form who are not salt losing, and 18 healthy siblings. Salt appetite was evaluated by questionnaire, preference tests, and dietary analyses. The findings showed that SW who were not therapeutically normalized showed increased salt appetite but no change in sweet preference. Their salt appetite correlated with symptoms of salt wasting, namely, plasma renin activity, plasma K(+), and urine Na(+) and (inversely) with blood pressure. Sensitivity to the taste of NaCl was not altered. Factor analyses of a larger group confirmed the distinction between salt appetite and sweet preference, but intake of dietary Na(+) and sweet carbohydrates and intake of salty and sweet snacks did not reflect distinct salt or sweet preferences. We confirm that putative perinatal dehydration, due to maternal nausea and vomiting during pregnancy, childhood vomiting, and diarrhea with occasional saline infusion, was related to increased salt appetite in adolescence. The findings suggest that salt appetite in humans is determined by interdependent, innate, physiological, and acquired attributes. Salt appetite in SW patients is an adaptive response mediated by the renin-angiotensin system, an innate predisposition to acquire salt preference (in anticipation of both sodium loss and its consequence), and imprinting by perinatal hyponatremic occurrences. Our findings contribute to understanding human salt intake, provide insight into the motivation for salt in patients with congenital adrenal hyperplasia 21-OH deficiency, and may point the way to improvements in therapeutic compliance in these patients.
 ...
PMID:Increased salt appetite in patients with congenital adrenal hyperplasia 21-hydroxylase deficiency. 1565 Jan 22

The recent advances in our understanding of immunology have greatly improved our knowledge about the natural history of autoimmune diseases and, in particular, of autoimmune Addison's disease (Autoimmune AD). Autoimmune AD is a chronic disorder with a long preclinical period marked by the presence of adrenal cortex autoantibodies (ACAs). In this chapter the main data on this will be analyzed. The populations with the highest risk of Autoimmune AD are first relatives of patients with AAD and patients with autoimmune diseases, particularly those with chronic hypoparathyroidism or with premature ovarian failure. The best markers to identify the subjects at risk are ACAs detected by the immunofluorescence test on human or animal tissues, or 21-hydroxylase autoantibodies (21-OHAbs) detected by radioimmunoassay (RIA). The evaluation of adrenal cortex function in these individuals includes the basal determination of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, plasma renin activity and cortisol after intravenous stimulation with synthetic ACTH. The multivariate analysis of the main factors (genetics, age, gender, titers of antibodies, pre-existing disease, status of the adrenal function) revealed that the risk of future AAD depends only on the presence of high antibody titers, chronic hypoparathyroidism or chronic candidiasis and adrenal dysfunction. On the basis of these parameters the risk of future Autoimmune AD can be calculated with an equation model. Patients with different risk scores need to be monitored at different time intervals, and those at high risk need to be strictly monitored and are the ideal subjects for future prevention trials.
 ...
PMID:Adrenal cortex autoantibodies in subjects with normal adrenal function. 1582 24

Systemic aldosterone plays an important role in the development of the microvascular disease and glomerular damage of the kidney in patients with diabetes mellitus and hyperlipidemia. Here, we investigated the possibility of local production of aldosterone in the kidney, using human primary glomerular mesangial cells. These cells produced both pregnenolone and aldosterone measured by specific radioimmunoassay and/or gas chromatography/mass spectrometry (GC/MS) methods. The production of both steroids was significantly stimulated by treatment with LDL, while angiotensin II had a synergistic effect. Adrenocorticotropic hormone (ACTH) and (Bu)2cAMP, on the other hand, failed to stimulate aldosterone production by these cells, suggesting that the local production of this steroid by mesangial cells is regulated differently from that of adrenal zona glomerulosa cells. Mesangial cells expressed the mRNA of the LDL receptor and steroidogenic enzymes, such as P450scc, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 21-hydroxylase and CYP11B2. Mesangial cells also expressed mRNA of the mineralocorticoid receptor (MR), and LDL stimulated its abundance by three-fold, while spironolactone, a completive antagonist of aldosterone, completely abolished this LDL effect. Since MR is a known mineralocorticoid-responsive gene as well as an intracellular receptor molecule for this steroid, these results suggest that locally produced aldosterone is biologically active, stimulating the transcription rates of the mineralocorticoid-responsive genes by activating the MR in mesangial cells. These pieces of evidence indicate that human mesangial cells are an aldosterone-producing tissue in which LDL plays a major regulatory role. Therefore, human renal mesangial endocrine system may contribute to local aldosterone concentrations and effects in the renal glomerulus independently of the systemic renin--angiotensin--aldosterone system and may participate in the development and progression of glomerular damage in several pathologic conditions.
 ...
PMID:Human renal mesangial cells produce aldosterone in response to low-density lipoprotein (LDL). 1599 78

We present a 39-year old female with a benign adrenal tumor characterized by autonomous secretion of cortisol, androgens, and aldosterone. The patient presented with a 4-year history of hypertension and severe hirsutism. Baseline investigations revealed elevated testosterone, androstendione, and 17OH progesterone with normal levels of dehydroepi androsterone sulfate. CT of the adrenals revealed a 2.5 x 3.0 cm tumor with characteristics of an adenoma on the left adrenal gland. Pelvic ultrasound was normal. Further investigations revealed suppressed basal ACTH levels, loss of diurnal rhythm of cortisol, and failure to suppress on low dose dexamethasone suppression test, suggesting autonomous cortisol secretion by the tumor. She had an exaggerated response of 17OH progesterone to ACTH, implying reduced 21-hydroxylase activity. An elevated plasma aldosterone concentration to plasma renin activity ratio was suggestive of hyperaldosteronism, which was confirmed by failure of aldosterone to suppress to a formal saline infusion test. Complete clinical and biochemical remission of the disease was observed after left adrenalectomy. Histology confirmed the presence of an adrenocortical adenoma. The patient developed multiple sclerosis 6 months after the operation. The flare-up of an autoimmune disease (multiple sclerosis) postoperatively could be coincidental or possibly related to the high normalization of the high cortisol levels acting as a precipitating factor.
 ...
PMID:A unique case of a benign adrenocortical tumor with triple secretion of cortisol, androgens, and aldosterone: development of multiple sclerosis after surgical removal of the tumor. 1661 21

Females with salt-wasting (SW) 21-hydroxylase deficiency (21OHD) may present with mild external genitalia virilization, despite complete or almost complete enzyme inactivation. We therefore analyzed genotype/phenotype correlation in 13 Japanese female patients with SW 21OHD. Criteria for classification into the SW phenotype included history of a salt-losing crisis with documented hyponatremia, hyperkalemia, and markedly elevated plasma renin activity. Urologists and pediatricians determined the Prader genital stage and classified the location of the vaginal entrance into the common urogenital sinus as low, moderate, or high. CYP21A2 gene, coding for 21-hydroxylase, was analyzed with Southern blotting and direct sequencing. Genotypes were categorized into four mutation groups, based on the degree of enzymatic activity (N, complete enzyme inactivation; groups A, < 2%, B, 3-7%, and C > 30%). Basal androgen levels were available from only six out of thirteen patients, so we could not relate androgen levels with the severity of external genitalia virilization. We compared the degree of external genitalia virilization with genotype. The severity of external genitalia virilization varied from Prader stage 1 to 4. One patient who presented with Prader 1 had a genotype consistent with Group B. In addition, discordance between Prader classification and the location of the vaginal entrance was noted; one patient classified as Prader 4 showed low vaginal entrance, while another patient classified as Prader 3 showed high vaginal entrance. The degree of the impairment of 21-hydroxylase activity does not correlate with the severity of virilization of the external genitalia in female patients with the SW type of 21OHD.
 ...
PMID:Severity of virilization of external genitalia in Japanese patients with salt-wasting 21-hydroxylase deficiency. 1867 8

In 75 young adults with diabetes mellitus type 1 (DM 1) we have performed a cross-sectional study to gain more information about their adrenocortical function. We have found in a surprisingly large portion of patients (25%) a subnormal response (<500 nmol/L, low responders) of the serum cortisol during low-dose Synacthen test, accompanied by significantly decreased stimulated values of aldosterone and salivary cortisol. Basal serum cortisol, aldosterone, and dehydroepiandrosterone sulphate (in women only) were significantly reduced in low responders as well, while ACTH, cortisol binding globulin, plasma renin activity, urinary free cortisol/24h, and salivary cortisol did not differ. The results indicate that the disorder of adrenocortical function in low responders occurs in all adrenocortical zones. The patients with the highest risk in respect to revealed hypocorticalism were DM 1 with autoimmune thyroiditis, 13 out of 36 in contrast to 5 out of 39 suffered from isolated form of DM 1, with onset around 30 years, independently on sex. The biorhythm of salivary cortisol in low responders under real-life conditions did not significantly differ from normal responders, except of the decreased values in the morning. Antibodies against 21-hydroxylase and adrenal cortex were negative in the entire group of diabetics studied. In conclusion, this is the first study to demonstrate in as much as 25% of young adults with DM 1 patients without any signs of adrenal autoimmunity decreased both basal and stimulated serum cortisol and aldosterone levels, implying existence of subclinical primary hypocorticalism.
 ...
PMID:Adrenocortical function in young adults with diabetes mellitus type 1. 2043 24

We demonstrated a rare case of bilateral aldosteronoma accompanied by secondary aldosteronism in a 37-year-old man with chronic renal failure on hemodialysis. He initially developed immunoglobulin A nephropathy at 11 years old, and had been treated with hemodialysis since the age of 17 years. His blood pressure was 110/68 mmHg, and no other abnormal findings were detected. Laboratory findings revealed that serum potassium was 3.9 mmol/L; plasma renin activity, 4.8 ng/ml/h and plasma aldosterone, 19,000 pg/mL. Abdominal computed tomography revealed bilateral adrenocortical tumors, measuring 34 and 40 mm in diameter in right and left tumors, respectively. (131)I-Adosterol scintigram showed bilateral accumulation. Left adrenalectomy was performed under laparoscopy. The tumor was encapsulated and well-circumscribed. The majority of the tumor was composed of a dark-brown portion admixed with sporadic foci of golden-yellow portions. Hyaline degeneration was detected in its central portion. The tumor was composed of clear cortical cells in viable portions. Tumor cells demonstrated immunoreactivity for the cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD II) and 21-hydroxylase, but not 17 alpha-hydroxylase. In the adjacent non-neoplastic adrenals, 3 beta-HSD II was markedly present in the hyperplastic glomerulosa zone. These findings suggest that the presence of secondary aldosteronism, which is closely related to the conditions of chronic renal failure on hemodialysis, eventually promoted the development of bilateral aldosteronoma from the zona glomerulosa hyperplasia.
 ...
PMID:Bilateral aldosteronoma associated with secondary aldosteronism in a chronic hemodialysis subject. 2051 19

Primary adrenocortical insufficiency, or Addison's disease (AD), results from an adrenal cortex hypofunction/dysfunction with a deficient production of glucocorticoids, mineralocorticoids and androgens, and with high levels of both ACTH and plasma renin activity. The prevalence of AD is 110-144 cases per million population in the developed countries. Autoimmune AD is the most frequent etiological form in adult patients, accounting for about 80% of cases, followed by post-tuberculosis AD in 10-15%, the remaining 5% being cases are due to vascular, neoplastic or rare genetic forms. Congenital adrenal hyperplasia is the most frequent form of AD in children and accounts for 72% of cases, whereas autoimmune AD is seen in around 10-15% of cases. The markers of autoimmune AD are adrenal cortex (ACA) or 21-hydroxylase autoantibodies (21-OHAbs) and they are present at diagnosis in more than 90% of cases. In autoimmune AD, the adrenal cortex is infiltrated by lymphocytes and plasma cells and the glands are sclerotic and reduced in volume. Autoimmune AD occurs mainly in middle-aged females, alone or associated with other (clinical, subclinical or potential) autoimmune diseases, giving rise to various forms of autoimmune polyglandular syndrome (type 1, 2 or 4). Replacement therapy with gluco-and mineralocorticoids is life-saving for patients with chronic adrenal insufficiency.
 ...
PMID:Autoimmune Addison's disease. 2116 69

Autoimmune Addison disease is a rare autoimmune disorder with symptoms that typically develop over months or years. Following the development of serum autoantibodies to the key steroidogenic enzyme, 21-hydroxylase, patients have a period of compensated or preclinical disease, characterized by elevations in adrenocortocotropic hormone and renin, before overt, symptomatic adrenal failure develops. We propose that local failure of steroidogenesis, causing breakdown of tolerance to adrenal antigens, might be a key factor in disease progression. The etiology of autoimmune Addison disease has a strong genetic component in man, and several dog breeds are also susceptible. Allelic variants of genes encoding molecules of both the adaptive and innate immune systems have now been implicated, with a focus on the immunological synapse and downstream participants in T lymphocyte antigen-receptor signaling. With the exception of MHC alleles, which contribute to susceptibility in both human and canine Addison disease, no major or highly penetrant disease alleles have been found to date. Future research into autoimmune Addison disease, making use of genome-wide association studies and next-generation sequencing technology, will address the gaps in our understanding of the etiology of this disease.
 ...
PMID:Autoimmune Addison disease: pathophysiology and genetic complexity. 2229 Mar 60


<< Previous 1 2 3 Next >>