SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
To determine if the adrenal gland plays a role in the thymic involution which occurs spontaneously in "lethargic" mutant mice, three different studies were made. Morphological studies were made first to determine if there was an indication of histological changes in the adrenal glands. Next, serum levels of corticosterone were measured by radioimmunoassay. Finally, mice were unilaterally adrenalectomized to see if such treatment would improve various symptoms of "lethargic" mutants. Results of the studies showed that lipid granules in the cortical cells of "lethargic"mutants were greatly reduced in number during the time of spontaneous thymic involution, and the mutant mice had a significantly higher level of serum corticosterone than the normal controls. Mutant mice unilaterally adrenalectomized at 15 days of age showed a marked improvement in their condition and their mortality rate decreased. It is concluded that spontaneous thymic involution of "lethargic" mutants is probably associated with adrenocortical hypersecretion.
Point mutations of ras genes (K-, H-, and N-ras) at codons 12, 13, and 61 and of the Gi2 alpha gene at codons 179 and 205, were studied in 56 primary adrenal cortical tumors and 6 adrenal cortical hyperplasias. Of 56 tumors, 24 were carcinomas and 32 were benign. The 24 carcinomas and 20 of the benign tumors were from American patients; the 12 remaining adenomas were from Japanese patients. Of the benign tumors 12 were cortisol-producing adenomas, 15 were aldosterone-producing adenomas, 3 were nonfunctioning adenomas, and 2 were adenomas that produced a virilizing syndrome. Tumor DNA obtained from archival formalin-fixed, paraffin-embedded tissue or fresh frozen tissue was amplified by polymerase chain reaction; and point mutations were detected by sequence-specific oligonucleotide hybridization. Activating ras mutations were found in 7 of 56 (12.5%) of all tumors: 3 of 24 (12.5%) carcinomas and 4 of 32 (12.5%) adenomas. Of adenomas from an American population, 4 of 20 (20%) exhibited positive ras mutations, whereas none was present in the Japanese tumors. All mutations detected were adenine to guanine transitions at the second position of N-ras codon 61, resulting in a conversion from glutamine to arginine. No mutations were found in K-ras or H-ras genes. Furthermore, no mutations of the Gi2 alpha gene were identified. These findings demonstrate that N-ras mutations at codon 61 may contribute to the genesis of both benign and malignant human adrenal cortical tumors. Finally, no mutations of the ras or Gi2 alpha genes were identified in hyperplastic adrenocortical tissues.
Explore the source record for details and available documents.
The case of a 39-year-old woman with Cushing's syndrome, hypertension and severe hypokalemia, caused by a unilateral adrenal adenoma composed of cells of the zona fasciculata histological type, is described. Plasma renin activity, plasma levels of mineralocorticoids and the aldosterone secretion rate were determined before and after surgical removal of the adenoma. The tumor appeared to produce autonomously cortisol as well as corticosterone, 18-hydroxycorticosterone and aldosterone. This condition has not previously been described in the literature and might be explained by strong expression of the full spectrum of activities of the mitochondrial enzyme P450 C11 by the tumor cells. Interestingly, despite hyperaldosteronism, plasma renin activity was not suppressed.
Distinguishing pituitary-dependent Cushing's disease from pseudo-Cushing's states can present a diagnostic challenge. Although many studies potentially discriminate between the 2, only the dexamethasone-suppressed corticotropin-releasing hormone (CRF) stimulation test at 15 minutes is 100% sensitive or specific. We measured baseline profiles of F and ACTH in 31 Cushing's disease patients, 11 with pseudo-Cushing's and 17 controls. Venous blood was collected at 30 minute intervals for 24-h. Subjects also had CRF stimulation tests and 2.0 mg/day dexamethasone suppression tests. F and ACTH profiles were analyzed for circadian rhythmicity, variability, and pulsatility. Relative circadian amplitude was decreased in Cushing's disease compared to both pseudo-Cushing's and normal states. Relative pulse amplitude was reduced in Cushing's disease. Because of this dampening of circadian and pulsatile variations, the overall variability of F and ACTH levels around their mean levels as quantified by the intra-series coefficient of variation (CV), was also decreased in Cushing's disease compared to pseudo-Cushing's and normal states. A F 24-h CV<40% was able to distinguish Cushing's disease from pseudo-Cushing's with 100% sensitivity (95% confidence interval (CI), 88-100%) and specificity (CI, 71-100%). An ACTH CV<40% had 97% sensitivity (CI, 83-100%) and 100% specificity (CI, 71-100%). An overnight 8-h F CV <40% also distinguished Cushing's disease from pseudo-Cushing's with 100% sensitivity (CI, 88-100%) and specificity (CI, 71-100%). These data show that a simple index of total temporal variability (the intra-series CV) derived from the analysis of basal F profiles, provides a useful method to distinguish Cushing's disease from pseudo-Cushing's. A F or ACTH CV <40% discriminates Cushing's disease from pseudo-Cushing's and reflects reduced circadian and pulsatile variations.
A case of unilateral adrenocortical hyperplasia is presented. A 46-year-old woman with a 7-year history of hypertension and a 1-year-history of hypokalemia was diagnosed with primary aldosteronism. Computed tomography, magnetic resonance imaging, venous sampling and adosterol scintigraphy exhibited a functioning left adrenal mass. The plasma aldosterone concentration increased markedly when furosemide with upright posture and either captopril or adrenocorticotropin were administered. Plasma renin activity was suppressed below the detectable range. Aldosterone secretion displayed a circadian rhythm and was not suppressed by dexamethasone administration. The resected left adrenal mass was pathologically diagnosed as adrenocortical nodular hyperplasia. Unilateral adrenal hyperplasia involving the zona glomerulosa rarely has been reported, with varying and incompletely characterized hormonal characteristics. This case report and literature review suggest unilateral adrenal hyperplasia as a rare cause of hyperaldosteronism with characteristics intermediate between idiopathic hyperaldosteronism and aldosterone-producing adrenocortical adenoma, resembling the functional features of the adenoma more closely.
Adrenocortical carcinoma is a rare tumor in children. This tumor is more likely to be hormonally active in children than in adults and tends to cause a variety of symptoms, which may mimic other benign endocrinopathies. These tumors are usually diagnosed at advanced stages and portend a dismal prognosis. We describe two cases of adrenocortical carcinoma. One child presented with Cushingoid symptoms secondary to hypercortisolism, including amenorrhea, hirsutism and weight gain. The other child presented with precocious puberty. Both children underwent resection of the tumors. We describe their presenting symptoms, postoperative course, adjuvant therapy and clinical course. Pertinent literature regarding the anatomy of the adrenal gland, pathology of adrenocortical carcinoma, factors influencing outcome, diagnostic modalities and treatment, are discussed.
The urinary corticoid:creatinine (c:c) ratio was determined in eight horses with hyperadrenocorticism (HAC). The mean (+/- SD) urinary c:c ratio of the eight horses with HAC (29 +/- 14 x 10(-6)) was significantly (P < 0.05) greater than the ratio in seven control horses (11 +/- 4.3 x 10(-6)). The urinary concentration of corticoids in control horses (201 +/- 60.4 nmol litre-1) was significantly (P < 0.05) lower than in horses with HAC (664 +/- 291 nmol litre-1). The urinary creatinine concentrations did not differ significantly (P > 0.05) between both groups. As both false negative and false positive cases were found, it is concluded that a measurement of the urinary c:c ratio in the horse should not be used as the sole test to confirm equine HAC.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Mitotane (o,p'-DDD; Lysodren) is the drug most commonly used to treat dogs with pituitary-dependent hyperadrenocorticism. Although variations of the original protocol, suggested more than 20 years ago, have been reported, most clinicians still use an initial loading dose of mitotane followed by a weekly maintenance dose. Although a gratifying response to treatment is seen in most dogs, some dogs are neither easy nor straightforward to treat and present the practitioner with one or more therapeutic challenges, including failure to respond adequately, development of adverse effects, or development of relapse during treatment. Nevertheless, with careful management and follow-up, such problems can be overcome and a successful outcome achieved in most cases.
In this chapter we have discussed the pathogenesis of canine PDH focusing on its relationship to aging, dopamine deficiency, and neurodegenerative disease. We have outlined the successful management of canine PDH patients with l-deprenyl, a selective MAO-B inhibitor. Treatment with l-deprenyl results in clinical and endocrinologic improvement (partial to complete) in approximately 83% of dogs, with improvement noted within the first 1 to 2 months of therapy. The safety profile of l-deprenyl is excellent, especially in light of the fact that the majority of patients are elderly. l-Deprenyl is a safe and effective first-line therapy for the medical management of uncomplicated cases of canine PDH.
In untreated hyperadrenocorticism, clinical problems may result from metastasis of an adrenocortical carcinoma, growth of a pituitary tumor, or complications associated with sustained hypercortisolemia itself, such as hypertension, cardiovascular disease, thromboembolism, glucose intolerance, and increased susceptibility to infection. This article discusses the origin, diagnosis, and treatment of the many complications associated with hyperadrenocorticism.
Explore the source record for details and available documents.
The amplitude and frequency of growth hormone (GH) secretory pulses are influenced by a variety of hormonal signals, among which glucocorticoids play an important role. The aim of this study was to investigate the pulsatile secretion pattern of GH in dogs in which the endogenous secretion of glucocorticoids is persistently elevated, i.e. in dogs with pituitary-dependent hyperadrenocorticism (PDH). Blood samples for the determination of the pulsatile secretion pattern of GH were collected at 10-min interval between 08:00 and 14:00 h in 16 dogs with PDH and in 6 healthy control dogs of comparable age. The pulsatile secretion patterns of GH were analyzed using the Pulsar program. GH was secreted in a pulsatile fashion in both dogs with PDH and control dogs. There was no statistical difference between the mean (+/-S.E.M.) basal GH level in dogs with PDH (0.7+/-0.1 microg/l) and the control dogs (0.6+/-0.1 microg/l). The mean area under the curve (AUC) for GH above the zero-level in dogs with PDH (4.6+/-0.6 microg/l per 6 h) was significantly lower than that in the control dogs (7.3+/-1.0 microg/l per 6 h). Likewise, the mean AUC for GH above the base-level in dogs with PDH (0.6+/-0.1 microg/l per 6 h) was significantly lower than that in the control dogs (3.7+/-1.0 microg/l per 6 h). The median GH pulse frequency in the dogs with PDH (2 pulses/6 h, range 0-7 pulses/6 h) was significantly lower (P = 0.04) than that (5 pulses/6 h, range 3-9 pulses/6 h) in the control group. The results of this study demonstrate that PDH in dogs is associated with less GH secreted in pulses than in control dogs, whereas the basal plasma GH concentrations were similarly low in both groups. It is discussed that the impaired pulsatile GH secretion in dogs with PDH is the result of alterations in function of pituitary somatotrophs and changes in supra-pituitary regulation.
Explore the source record for details and available documents.