Hormone pulsatility discrimination via coarse and short time sampling.
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Pulsatile hormonal secretion is a ubiquitous finding in endocrinology. However, typical protocols employed to generate data sets suitable for "pulsatility analysis" have required 60-300 samples, rendering such studies largely research methodologies, due primarily to considerable assay expense. One successful mathematical strategy in calibrating changes in pulsatility modalities is approximate entropy (ApEn), a quantification of sequential irregularity. Given the degree of differences between ApEn values in pathophysiological subjects vs. healthy controls reported in several recent studies, we queried to what extent coarser (less frequent) and shorter duration time sampling would still retain significant ApEn differences between clinically distinct cohorts. Accordingly, we reanalyzed data from two studies of 24-h profiles of healthy vs. tumoral hormone secretion: 1) growth hormone comparisons of normal subjects vs. acromegalics, originally sampled every 5 min; and 2) ACTH and cortisol comparisons of normal subjects vs. Cushing's disease patients, originally sampled every 10 min. By multiple statistical analyses, we consistently and highly significantly (P < 0.0001) established that serum concentration patterns in tumor patients are more irregular than those of controls, with high sensitivity and specificity, even at very coarse (e.g., 60 min) sampling regimens and over relatively short (2-4 h) time intervals. The consistency of these findings suggests a broadly based utility of such shorter and/or coarser sampling methodologies. Substantial reduction in sampling requirements holds the potential to move analysis of pulsatile hormone release from a primarily research tool to a clinically applicable protocol, in appropriate diagnostic and therapeutic contexts. (+info)
Calcium-stimulated insulin secretion in diffuse and focal forms of congenital hyperinsulinism.
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OBJECTIVES: To identify infants with hyperinsulinism caused by defects of the beta-cell adenosine triphosphate-dependent potassium channel complex and to distinguish focal and diffuse forms of hyperinsulinism caused by these mutations. STUDY DESIGN: The acute insulin response to intravenous calcium stimulation (CaAIR) was determined in 9 patients <20 years with diffuse hyperinsulinism caused by defective beta-cell sulfonylurea receptor (SUR1(-/-)), 3 patients with focal congenital hyperinsulinism (6 weeks to 18 months), a 10-year-old with insulinoma, 5 with hyperinsulinism/hyperammonemia syndrome caused by defective glutamate dehydrogenase (6 months to 28 years), 4 SUR1(+/-) heterozygotes with no symptoms, and 9 normal adults. Three infants with congenital focal disease, 1 with diffuse hyperinsulinism, and the child with insulinoma underwent selective pancreatic intra-arterial calcium stimulation with hepatic venous sampling. RESULTS: Children with diffuse SUR1(-/-) disease and infants with congenital focal hyperinsulinism responded to CaAIR, whereas the normal control group, patients with hyperinsulinism/hyperammonemia syndrome, and SUR1(+/-) carriers did not. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling revealed selective, significant step-ups in insulin secretion that correlated anatomically with the location of solitary lesions confirmed surgically in 2 of 3 infants with congenital focal disease and in the child with insulinoma. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling demonstrated markedly elevated baseline insulin levels throughout the pancreas of the infant with diffuse hyperinsulinism. CONCLUSIONS: The intravenous CaAIR is a safe and simple test for identifying infants with diffuse SUR1(-/-) hyperinsulinism or with focal congenital hyperinsulinism. Preoperative selective arterial calcium stimulation of the pancreas with hepatic venous sampling can localize focal lesions causing hyperinsulinism in children. The combination of these calcium stimulation tests may help distinguish focal lesions suitable for cure by local surgical resection. (+info)
Trypsin-based laboratory methods and carboxypeptidase activation peptide in acute pancreatitis.
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Acute pancreatitis is a common disease varying widely in severity. At present, there is no "gold standard" for the diagnosis of acute pancreatitis. Currently, the diagnosis of acute pancreatitis is based on measurements of serum amylase and/or lipase activity, which are considered unsatisfactory due to their low level of accuracy. Early identification of acute pancreatitis and especially detection of patients with a severe form of the disease is of utmost importance. Premature intrapancreatic activation of trypsinogen is a crucial early event in the pathophysiology of acute pancreatitis. The conversion of trypsinogen to active trypsin is mediated by the release of its activation peptide (TAP). The active trypsin is then able to activate other pancreatic zymogens (i.e. procarboxypeptidase) leading to tissue damage and eventually to autodigestion of the pancreas. To improve the laboratory diagnostics of AP, new methods have been developed to measure this primary pancreatic proteolytic insult. Here we review the current knowledge and clinical implications of trypsin based laboratory methods and carboxypeptidase activation peptide (CAPAP) in the diagnosis and severity assessment of acute pancreatitis. (+info)
Preclinical Cushing's syndrome due to ACTH-independent bilateral macronodular adrenocortical hyperplasia with excessive secretion of 18-hydroxydeoxycorticosterone and corticosterone.
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A 64-year-old woman developed hypertension and hypokalemia, due to ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) with excessive secretion of 18-hydroxydeoxycorticosterone and corticosterone. Plasma cortisol did not show a diurnal rhythm, and was not suppressed by dexamethasone (8 mg). Plasma cortisol responded to ACTH and was increased by hypoglycemia without modifying ACTH levels. Radiological studies demonstrated that adrenal glands were enlarged with macronodules. Although the patient exhibited a low plasma renin activity and aldosterone levels, hypokalemia and hypertension were observed. Hormonal findings would support the hypothesis that the tumor of AIMAH originated from cells of the upper zona fasciculata. (+info)
An audit of the insulin-tolerance test in 255 patients with pituitary disease.
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OBJECTIVE: The insulin-tolerance test (ITT) is currently considered to be the gold standard for evaluating adults suspected of GH deficiency (GHD). The aim of this study was to determine factors that may influence nadir blood glucose (BG) when using a mean insulin dose of 0.1 IU/kg body weight. Furthermore, we wanted to evaluate the safety and GH-related aspects of the ITT. DESIGN: ITT was performed in 277 patients, of whom 255 (129 females) were eligible for evaluation. RESULTS: Multiple regression analysis, including the whole population, showed that the major determining factors for nadir BG were basal BG and body mass index (BMI) (P<0.02). No serious adverse event was recorded. Sixty-three percent of all patients tested had severe GHD with peak GH response to hypoglycaemia below 7.8 mIU/l. The positive predictive value for IGF-I was 0.82 and the negative predictive value was 0.47, using a cut-off value corresponding to -2 s.d. GH peak response to hypoglycaemia decreased with increasing numbers of other pituitary hormone deficiencies. CONCLUSIONS: When determining the dose of insulin based on weight, factors like pre-test BG and BMI should also be considered. We propose an algorithm stating that the dose of insulin should be 0.1 IU insulin/kg body weight minus 2 IU if pre-test BG is <4.0 mmol/l and minus 2 IU if BMI is <20 kg/m(2) in order to take these factors into account. Our findings furthermore support the concept that the low-dose ITT is a safe test in adults, when performed in experienced hands. It was confirmed that IGF-I is not sufficient when diagnosing GHD in adults, and reliable stimulation tests like ITT are required in the diagnosis. (+info)
Isolated adrenocorticotropin deficiency presenting with impaired renin-angiotensin-aldosterone system and suppressed parathyroid hormone-vitamin D axis.
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We report here a 47-year-old woman with isolated adrenocorticotropin (ACTH) deficiency (IAD). She presented impaired renin-angiotensin-aldosterone (R-A-A) system and suppressed parathyroid hormone (PTH)-vitamin D system. She showed severe hyponatremia due to secondary adrenocortical insufficiency, which was deteriorated by hypoaldosteronism. She also showed hyperphosphatemia and relative hypercalcemia with suppressed PTH-vitamin D axis. Moreover, she showed hypothyroidism, which was thought to be important to maintain normal Ca levels under secondary hypoadrenalism via decrease in bone resorption by T3. Replacement with glucocorticoid completely normalized PTH-vitamin D axis and R-A-A system. Thus, the present case implicates that severe adrenocortical deficiency due to IAD might affect both R-A-A system and PTH-vitamin D axis. These findings suggest that the ACTH-cortisol axis has an important role in mineral metabolism in vivo. (+info)
Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve.
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A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 microg corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (+info)
Phaeochromocytoma by way of case reports.
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Endocrine causes of hypertension are relatively rare, but their detection offers a real chance for cure. This is particularly true of phaeochromocytoma, a catecholamine-producing tumour derived from chromaffin tissue, which, if left undetected, is invariably fatal. The lethal nature of this tumour is dependent on two major characteristics: firstly, its ability to secrete catecholamines in excess, resulting in potentially catastrophic consequences; and, secondly, its malignant potential. Approximately 5-10% of these tumours are malignant, which, if metastasised, are generally refractory to treatment. Clearly, however, because only one in 1,000 hypertensives is likely to harbour a phaeochromocytoma, it is not cost-effective option to screen all hypertensives for this cause. Rather, a selective approach is preferred in which a high index of suspicion for the clinical characteristics of this tumour is used to guide the physician. The following two case reports derived from our records at Chris Hani Baragwanath Hospital will illustrate many issues related to diagnosis and management of this fascinating tumour. (+info)