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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of hypercortisolemia and ACTH on the metabolism of cortisol in congenital adrenal hyperplasia, Cushing's syndrome, and exogenous ACTH and cortisol administration were investigated by analysis of the respective urinary tetrahydro-metabolites of cortisol (THF and aTHF) and cortisone (THE) by capillary gas chromatography. The results for the patients with congenital adrenal hyperplasia establish that ACTH hypersecretion in the absence of an associated marked elevation of plasma cortisol does not cause inhibition of the 11beta-OHSD enzyme. In contrast elevated plasma cortisol levels (adrenal adenoma or intravenous cortisol administration) in the presence of suppressed ACTH secretion leads to significant inhibition of the peripheral conversion of cortisol to cortisone. The latter results are equivalent to the mode of cortisol metabolism noted during clinical states of ACTH hypersecretion and hypercortisolemia (Cushing's disease, ectopic ACTH syndrome and ACTH administration). The overall findings provide convincing evidence that ACTH hypersecretion is not associated with specific in vivo inhibition of 11beta-OHSD enzyme activity.
Exp Clin Endocrinol Diabetes 1998
PMID:Effect of hypercortisolism and ACTH on the metabolism of cortisol. 951 61

A 51-year-old female patient, with an adrenocorticotrophic hormone-secreting pituitary tumor, was scheduled for transphenoidal hypophysectomy. She had a history of recent onset diabetes mellitus and a 2-year history of arterial hypertension. Despite ongoing medical therapy, preoperative blood pressure was 150-160/90-120 mm Hg. During general anesthesia, in response to perinasal infiltration with 10 ml of a solution containing lidocaine 200 mg and epinephrine 100 microg, blood pressure increased from 144/80 mm Hg to 317/175 over 3 minutes, as assessed by direct blood pressure monitoring. At the completion of the anesthetic, as the patient awakened and coughed and moved, blood pressure again increased dramatically, this time from 154/87 mm Hg to 285/170 over 3 minutes. Five months postoperatively, the patient's serum cortisol concentrations had normalized and her cuff blood pressure was 126/82, despite a reduction in her antihypertensive medications. The dramatic intraoperative blood pressure changes in this patient were attributed to the effects of hypercortisolemia on the normal physiologic responses to epinephrine and patient movement.
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PMID:Exaggerated hemodynamic responses to nasal injection and awakening from anesthesia in a Cushingoid patient having transsphenoidal hypophysectomy. 1090 71

Three patients with functional adrenal tumors, Cushing's syndrome, primary aldosteronism and pheochromocytoma, who underwent adrenalectomy and were subsequently cured, were studied. All these patients had been treated for diabetes for several years before the diagnosis of adrenal tumors. In each case the state of diabetes before and after surgery, including parameters of insulin secretion and insulin resistance, was compared to demonstrate how the adrenal disorder influenced the nature of diabetes. In the case of Cushing's syndrome the hypercortisolemia caused insulin resistance in the peripheral tissues. In the case of primary aldosteronism, excessive production of aldosterone diminished insulin secretion possibly through hypokalemia. Pheochromocytoma affected both insulin secretion and insulin sensitivity through hypersecretion of catecholamines. In all these patients the adrenal tumors were found in clinical contexts other than management of diabetes itself. By careful retrospective review of these three patients' history, several important points that might have drawn the physician's attention to the underlying adrenal disorders were pointed out. These included past history of acute myocardial infarction with onset at unexpectedly young age in the case of Cushing's syndrome and unexpectedly high insulin resistance for the patient's body mass index in the case of pheochromocytoma.
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PMID:Three patients with adrenal tumors having been treated simply for diabetes mellitus. 1091 24

Chronic severe hypercortisolism is associated with life-threatening infections, diabetes and a high surgical mortality rate. Oral medical therapy can inhibit steroidogenesis and reduce the risk of these complications. However, apart from a few reports using an ethyl alcohol formulation of the iv anesthetic etomidate, there is no well-tested parenteral steroidogenesis inhibitor. We used the propylene glycol preparation of etomidate available in the United States to control hypercortisolism in a 39-yr-old man with ectopic ACTH secretion who was unable to take oral medications. Etomidate was administered over a period of 5.5 months. We titrated the dose of etomidate daily using serum cortisol levels, to avoid steroid over replacement and allow for a response to ongoing stress. A reduced dose during a period of acute renal failure achieved adequate control of hypercortisolemia. Suppression of steroidogenesis persisted for at least 14 d and perhaps as long as 6 wk after cessation of the medication. Except for transient myoclonus, the patient tolerated this preparation well. Parenteral propylene glycol containing etomidate can be used safely for a prolonged period to reduce hypercortisolemia in patients unable to take oral medications.
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PMID:Use of a parenteral propylene glycol-containing etomidate preparation for the long-term management of ectopic Cushing's syndrome. 1154 33

Insulin resistance is a condition of central importance in a cluster of clinical disorders including diabetes mellitus, hypertension, dyslipidemia, central obesity and coronary heart disease. Despite its association with numerous health problems, the mechanism responsible for the development of this phenomenon remains to be established. A novel theory has proposed that insulin resistance in diabetes stems, at least in part, from enhanced free fatty acid (FFA) oxidation and/or excessive production of glucocorticoids (GCs). Several key predictions of this premise were subjected to experimental testing using streptozotocin (STZ)-treated rats as a model for insulin-dependent diabetes mellitus and euglycemic-hyperinsulinemic clamp technique for the in vivo measurement of insulin actions. Euglycemic clamp studies with an insulin infusion index of 5 mU/kg/min were used to measure endogenous glucose production (EGP), glucose infusion rate (GIR), glucose disposal rate (GDR) and skeletal muscle glucose utilization index (GUI). Post-absorptive basal EGP and plasma levels of glucose and free fatty acids (FFA) were elevated in the STZ diabetic rats compared to their corresponding control values. In contrast, hypoinsulinemia was evident in these animals. Steady-state GIR and GDR during euglycemic-hyperinsulinemic clamp were markedly decreased in the STZ diabetic rats. Similarly, insulin-mediated suppression of EGP and plasma FFA concentration was also impaired in these animals. GUI, a measure of 2-deoxyglucose (2-DG) uptake, was increased in response to insulin in the order of white gastrocnemus (WG), red gastrocnemus (RG), extensor digitorum longus and soleus muscles. This parallels the percentage of red fibers in these muscles. Diabetes interferes with insulin's ability to increase 2-DG uptake in all of the above muscles with the exception of WG. Nullification of the associated hyperlipidemic and hypercortisolemic states of diabetes with etomoxir (hyperlipidemic) and the glucocorticoid receptor blocker RU-486 (hypercortisolemic) ameliorated the diabetes-related impairment of the in vivo insulin action. Overall these results together with those garnered from the literature support the notion that hypercortisolemia and the enhancement of FFA oxidation are involved, at least in part, in the development of hepatic and skeletal muscle insulin resistance in poorly controlled type I diabetes.
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PMID:Co-administration of etomoxir and RU-486 mitigates insulin resistance in hepatic and muscular tissues of STZ-induced diabetic rats. 1160 76

Cushing's syndrome results from prolonged exposure to excessive circulating glucocorticosteroids, and is associated with significant morbidity and mortality. While the treatment of choice in most patients is surgical, the metabolic consequences of the syndrome, including increased tissue fragility, poor wound healing, hypertension, and diabetes mellitus, increase the risks of such surgery. The hypercortisolemia and its sequelae can be efficiently reversed using medical therapy, either as a temporary measure prior to definitive treatment, or longer term in more difficult cases. Drug treatment has been targeted at the hypothalamic/pituitary level, the adrenal glands, and also at the glucocorticoid receptor level. In this review we discuss the pharmacotherapeutic agents that have been used in Cushing's syndrome, and their efficacy, the monitoring of treatment, and potential therapies that may prove useful in the future in this complex endocrinological disorder.
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PMID:The medical management of Cushing's syndrome. 1238 47

Patients suffering from diabetes mellitus and depressive patients show a hyperactivity of the hypothalamic-pituitary-adrenocortical axis (HPA-axis) with hypercortisolemia. Hypercortisolemia is associated with cognitive dysfunction. These neuroendocrinological disturbances can cause an insulin resistance syndrome which complicates the regulation of blood glucose. Cognitive and depressive disorders in patients with diabetes mellitus might be associated with a hyperactivity of the HPA-axis. By normalising the HPA-axis both disorders could be improved. In addition, one can expect that antidepressive treatment with normalization of the HPA-axis could improve the metabolic situation and cognitive dysfunction. There is need for further research to study the associations between depression, diabetes mellitus and cognitive dysfunction.
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PMID:[The HPA-axis as a possible link between depression, diabetes mellitus and cognitive dysfunction]. 1252 32

Visceral obesity represents an important risk factor associated with hypertension, diabetes and cardiovascular diseases. Since this condition is associated with a disruption of the functioning of the HPA axis, stress-induced HPA axis activation has been identified to play an important role in this preferential body fat accumulation. HPA axis activation increases cortisol (corticosterone) production which has been shown to exert hyperphagic and antithermogenic effects. Since abdominal adipose tissue has more cells per mass units, higher blood flow and more glucocorticoid receptors, glucocorticoids affect abdominal fat to a greater extent than subcutaneous adipose tissue. Cushing's syndrome in humans is the best evidence showing a link between hypercortisolemia and accumulation of central fat. The Hervey's hypothesis which suggests that fat cells take up and catabolize glucocorticoids is one of the possible regulatory effect that supports the adaptive role of visceral fat in response to stress. This is also supported by other evidence showing that abdominal obesity is associated with an increased cortisol clearance. Hormonal and enzymatic changes have been implicated in this preferential body fat accumulation in response to stress. Specific genetic background may also accentuate this visceral fat accumulation in some individuals exposed to stress. Alternatively, obesity could also be a source of stress promoting the visceral fat accumulation since visceral fat is able to release cytokines which stimulate the HPA axis. Even if the available literature does not permit to establish clearly which comes first, it suggests that visceral obesity could represent a non optimal physiological adaptation to stress. In this context, visceral obesity treatment should focus on stress management and weight loss strategies in order to stop this vicious circle.
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PMID:Is visceral obesity a physiological adaptation to stress? 1461 17

Hyperadrenocorticism is a rare syndrome in cats. Current medical therapy is unsatisfactory and prognosis for long-term survival with surgical treatment is guarded. We report on 5 cats treated with the 3-beta hydroxysteroid dehydrogenase inhibitor trilostane. Diagnosis was confirmed in all cats by endocrine testing. Three cats had concurrent diabetes mellitus. Trilostane reduced clinical signs and improved endocrine test results in all cats, but insulin requirements did not change and all continued to have some signs of hypercortisolemia. Two died or were euthanized after 16 and 140 days, whereas 3 were still alive 6, 11, and 20 months after the start of trilostane therapy. Trilostane ameliorates clinical signs of feline hyperadrenocorticism, but more research is needed before it can be recommended for treatment.
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PMID:Trilostane therapy for treatment of pituitary-dependent hyperadrenocorticism in 5 cats. 1505 66

We present an unusual patient who simultaneously had severe renal artery stenosis RAS and Cushing's syndrome. The case highlights the difficulty of reaching a specific diagnosis of Cushing's syndrome and the possible interaction between Cushing's syndrome and some other concurrent illnesses that this patient had. A 37-year old man presented with severe hypertension HTN and uncontrolled diabetes mellitus DM without clear physical signs of Cushing's syndrome. He was found to have severe osteoporosis, proximal myopathy, several cutaneous warts, tinea versicolor, and chronic viral hepatitis. Captopril-stimulated renal scan and renal artery angiogram revealed severe RAS. Partial balloon dilatation of RAS led to improvement in HTN. Unexpectedly, urine free cortisol 24 hour was found extremely high. Serum adrenocorticotropic hormone ACTH was also elevated and high dose dexamethasone suppression tests were inconclusive. Several imaging studies failed to localize the source of ACTH. Despite normal MRI of the pituitary gland, bilateral inferior petrosal sinus sampling IPSS localized the source of ACTH secretion to the right side of the pituitary gland and right anterior hemihypophysectomy resulted in cure of Cushing's disease, HTN, DM, and tinea versicolor with significant improvement in cutaneous warts, osteoporosis, and chronic hepatitis. In conclusion, RAS and Cushing's syndrome may occur together. Significant hypercortisolemia can occur without clear signs of Cushing's syndrome. Controlling hypercortisolemia is of paramount importance when treating chronic infections in patients with Cushing's syndrome.
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PMID:Severe hypertension secondary to renal artery stenosis and Cushing's syndrome. 1590 Mar 83


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