1/73. prevalence of mild apparent mineralocorticoid excess in Mennonites.We have studied an unusual patient with mild low-renin hypertension due to a homozygous mutation in the HSD11B2 gene (PNAS 95:10200-10205, 1998). The patient came from an inbred Mennonite family, and though the mutation identified her as an AME patient, she had a normal birth weight and did not demonstrate the typical features of AME, such as hypokalemic alkalosis, low birth weight, failure to thrive, poor growth, and in many cases nephrocalcinosis. Biochemically, typical patients with AME have abnormal cortisol metabolites and an exceedingly diminished ability to convert [11-3H]cortisol to cortisone. In this patient with mild AME, the conversion of cortisol to cortisone was 58% compared to 0 to 6% in typical AME patients, while the normal conversion is 90 to 95%. Molecular analysis of the HSD11B2 gene of this patient showed a homozygous mutation in codon 227 (P227L). We studied this Mennonite population for the prevalence of the P227L mutation. Our hypothesis was that this mild form of AME would be prevalent in the somewhat inbred Mennonite population to which the patient belongs. Our proposed study was 1) to determine if there are other cases of this mild form of AME, and 2) to establish the heterozygote frequency of the mutation in the Mennonites. RESULTS: We did not detect any additional cases of mild AME. We detected 15 carriers of the P227L mutation out of 445 Mennonites, resulting in a heterozygote frequency of 0.03. CONCLUSION: Since this is an inbred population, the chance of two heterozygotes marrying would be 0.001, which is 1 in 1000 people. This population is known to have large families and therefore the possibility of having an affected child is high. The population consists of 2000 members and we have discovered one affected patient. Thus, there might be one other patient in this population.- - - - - - - - - - ranking = 1keywords = hypokalemic alkalosis, alkalosis, hypokalemic (Clic here for more details about this article) |
2/73. Saline-resistant metabolic alkalosis, severe hypokalemia and hypertension in a 74-year-old woman.The case of a 74-year-old woman with past history of hypertension and cerebrovascular accident admitted with pneumonia, dehydration, hypernatremia and severe hypokalemic alkalosis is presented. After correction of the hypertonic dehydration, the hypokalemia and alkalosis persisted in spite of aggressive potassium supplementation and the patient became hypertensive. Mineralocorticoid excess was suspected and excluded after extensive endocrinological testing. The use of aldactone failed to revert the abnormalities. triamterene administration corrected the electrolytes and acid base aberrations, and dramatically improved the blood pressure control. This clinical picture is compatible with the diagnosis of Liddle's syndrome. Our patient exemplifies the unique occurrence of hypokalemic metabolic alkalosis in association with volume contraction at the start of the hospitalization and volume expansion later on her course.- - - - - - - - - - ranking = 1.1434394732187keywords = hypokalemic alkalosis, alkalosis, hypokalemic (Clic here for more details about this article) |
3/73. Severe hypertension induced by the long-acting somatostatin analogue sandostatin LAR in a patient with diabetic autonomic neuropathy.A 26-yr-old woman with type 1 diabetes and severe symptomatic autonomic neuropathy was treated with the long-acting somatostatin analogue Sandostatin LAR for intractable diarrhea. Her diarrhea had previously been successfully managed with three daily injections of octreotide without adverse consequences. She was given a single dose of Sandostatin LAR and within 2 weeks reported the development of increasingly frequent and severe headaches. Three weeks after the injection, she was admitted to hospital with severe hypertension, which eventually resolved with the administration of antihypertensive agents. No other underlying cause of the hypertension was discovered. Rechallenge of the patient with octreotide resulted in a transient hypertensive episode, which lasted 3 h. Severe hypertension, therefore, seems to be a possible adverse effect of treatment of diabetic diarrhea with somatostatin analogues, which should be used with great caution in subjects with severe autonomic dysfunction.- - - - - - - - - - ranking = 0.0022582344928913keywords = diarrhea (Clic here for more details about this article) |
4/73. Liddle's syndrome: a report in a middle-aged woman.A 54-year-old woman with diabetes mellitus was hospitalized with generalized edema and weakness. She was also found to have hypertension, hypokalemia and metabolic alkalosis. Detailed examination showed subnormal plasma renin activity and plasma aldosterone concentration. Adrenal CT scanning revealed no adrenal tumor. A successful treatment with amiloride established the diagnosis of Liddle's syndrome for the patient. Liddle's syndrome, a rare hereditary disease usually found in young patients, should be considered in the differential diagnosis of hypertension even in elderly individuals.- - - - - - - - - - ranking = 0.020981846673094keywords = alkalosis (Clic here for more details about this article) |
5/73. loperamide therapy in a patient with diarrhea and resistant hypertension.A 65-year-old man was admitted to our hospital for resistant essential hypertension. He had a past history of bowel resections due to Crohn's disease. We assumed that in this patient insufficient drug absorption might be a cause of resistant hypertension and that even increased antihypertensive regimens would fail to decrease blood pressure. We administered loperamide, which may increase drug absorption from the residual intestine. blood pressure was successfully decreased, with a concomitant increase in blood concentration of antihypertensive drugs. In patients with impaired drug absorption, we should make an effort to restore drug obstruction before considering increased drug regimens.- - - - - - - - - - ranking = 0.0030109793238551keywords = diarrhea (Clic here for more details about this article) |
6/73. angioedema of the small bowel due to an angiotensin-converting enzyme inhibitor.We describe a case of a 72-year-old woman who presented with two episodes of abdominal pain, vomiting, and diarrhea. Abdominal computed tomographic scans done during each episode demonstrated edema of the small bowel. review of the patient's history revealed that she had been started on a treatment of lisinopril for hypertension 1 month before the first episode and had her prescribed dose increased 24 hours before each presentation. Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema was suspected and the medication was discontinued. The patient has remained symptom-free while not taking the ACE inhibitor for 1 year. review of the literature reveals only nine similar cases. All cases, including ours, occurred in women. angioedema of the small bowel associated with ACE inhibitors is rare and often is not recognized before surgical exploration. angioedema of the gastrointestinal tract should be considered in symptomatic patients taking ACE inhibitors.- - - - - - - - - - ranking = 0.00075274483096377keywords = diarrhea (Clic here for more details about this article) |
7/73. nephrocalcinosis and renal cysts associated with apparent mineralocorticoid excess syndrome.Apparent mineralocorticoid excess (AME) syndrome is a rare inherited disorder caused by 11beta-hydroxysteroid dehydrogenase (11-HSD 2) isozyme deficiency in the kidney. This enzyme is responsible for oxidizing cortisol to its inactive metabolite cortisone. An elevated tetrahydrocortisol (THF) and allotetrahydrocortisol (aTHF) to tetrahydrocortisone (THE) ratio in the urine is pathognomonic of AME syndrome. Clinical features include hypertension, hypokalemia, alkalosis, reduced plasma renin activity (PRA), low aldosterone levels, and occasionally nephrocalcinosis. Here we describe a 13-year-old boy who presented with severe hypertension, hypokalemia, low PRA and aldosterone levels, and elevated THF plus aTHF/THE ratio in the urine consistent with a diagnosis of AME syndrome. On ultrasound examination, he had severe nephrocalcinosis, and bilateral renal cysts. Renal cysts have not been previously reported in AME syndrome. The development of nephrocalcinosis and renal cysts may be associated with chronic long-standing hypokalemia. An early diagnosis and treatment of AME syndrome could help to prevent these sequelae, and to preserve renal function.- - - - - - - - - - ranking = 0.020981846673094keywords = alkalosis (Clic here for more details about this article) |
8/73. Approach to the patient with hypertension, unexplained hypokalemia, and metabolic alkalosis.We present a patient with hypertension and hypokalemia secondary to an aldosterone-producing adenoma that was renin responsive (APARR). We discussed the sequential approach to the diagnosis of the different subtypes of primary aldosteronism and confirmed the presence of an APARR. The most common cause of primary aldosteronism is an aldosteronoma; functionally, these adenomas respond poorly to angiotensin ii but show a brisk response to adrenocorticotropin hormone. They have a pattern of aldosterone level that declines in parallel with cortisol levels. Our patient had an APARR, with an increase of aldosterone in the upright posture. The unusual physiologic response, incidence, and clinical characteristics of APARR are reviewed.- - - - - - - - - - ranking = 0.083927386692376keywords = alkalosis (Clic here for more details about this article) |
9/73. A mutation in the cofactor-binding domain of 11beta-hydroxysteroid dehydrogenase type 2 associated with mineralocorticoid hypertension.Renal 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) is an enzyme responsible for the peripheral inactivation of cortisol to cortisone in mineralocorticoid target tissues. Mutations in the gene encoding 11betaHSD2 cause the syndrome of apparent mineralocorticoid excess (AME), an autosomal recessive form of inherited hypertension, in which cortisol acts as a potent mineralocorticoid. The mutations reported to date have been confined to exons 3-5. Here, we describe two siblings, 1 and 2 yr old, who were diagnosed with hypokalemic hypertension and low plasma aldosterone and renin levels, indicating mineralocorticoid hypertension. Analysis of urinary steroid metabolites showed a markedly impaired metabolism of cortisol, with (tetrahydrocortisol 5alpha-tetrahydrocortisol)/tetrahydrocortisone ratios of 40-60, and nearly absent urinary free cortisone. Although phenotypically normal, the heterozygous parents showed a disturbed cortisol metabolism. Genetic analysis of the HSD11B2 gene from the AME patients revealed the homozygous deletion of six nucleotides in exon 2 with the resultant loss of amino acids Leu(114) and Glu(115), representing the first alteration found in the cofactor-binding domain. The deletion mutant, expressed in HEK-293 cells, showed an approximately 20-fold lower maximum velocity but increased apparent affinity for cortisol and corticosterone. In contrast, two additionally constructed substitutions, Glu(115) to Gln or Lys, showed increased maximal velocity and apparent affinity for 11beta-hydroxyglucocorticoids. Functional analysis of wild-type and mutant proteins indicated that a disturbed conformation of the cofactor-binding domain, but not the missing negative charge of Glu(115), led to the observed decreased activity of the deletion mutant. Considered together, these findings provide evidence for a role of Glu(115) in determining cofactor-binding specificity of 11betaHSD2 and emphasize the importance of structure-function analysis to elucidate the molecular mechanism of AME.- - - - - - - - - - ranking = 0.017548393180093keywords = hypokalemic (Clic here for more details about this article) |
10/73. hypokalemia, metabolic alkalosis, and hypertension: Cushing's syndrome in a patient with metastatic prostate adenocarcinoma.Ectopic adrenocorticotropic hormone (ACTH) and/or corticotropin-releasing hormone (CRH) are associated with a growing list of tumors. We report a 69-year-old white man with a history of high-grade prostate carcinoma and widely metastatic adenocarcinoma who presented with metabolic alkalosis, hypokalemia, and hypertension secondary to ectopic ACTH and CRH secretion. Laboratory values were consistent with hypokalemia and metabolic alkalosis. Markedly elevated serum cortisol (135 microg/dL), ACTH (1,387 pg/dL), CRH (69 pg/dL), and urine free cortisol (16,276 microg/24 h) levels were found. Chest computed tomographic (CT) scan showed small noncalcified parenchymal densities; however, bronchoscopy and bronchoalveolar lavage washings were unremarkable for a neoplastic process. Abdominal CT scan and magnetic resonance imaging showed multiple small liver lesions and multiple thoracic and lumbar intensities consistent with diffuse metastatic disease. Histological analysis of a biopsy specimen from the thoracic spine showed an undifferentiated adenocarcinoma consistent with a prostate primary tumor. The severe metabolic alkalosis secondary to glucocorticoid-induced excessive mineralocorticoid activity was treated with potassium supplements, spironolactone, and ketoconazole. In this case report, we describe an unusual tumor associated with ectopic ACTH and CRH production and the pharmacodynamic relationship of plasma cortisol levels and urinary cortisol excretion with ketoconazole treatment.- - - - - - - - - - ranking = 0.14687292671166keywords = alkalosis (Clic here for more details about this article) |
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