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PubMed2005

Glucocorticoid resistance and hypersensitivity.

This article emphasizes the disorders caused by mutations and polymorphisms of the alpha form of the glucocorticoid receptor. These disorders usually present with increased circulating cortisol concentrations and must be distinguished from Cushing's syndrome, because the therapies are markedly different. The other disorders present with clinical features limited to a specific organ system. Although they illustrate important physiologic and pathophysiologic principles, they usually are not confused with Cushing's syndrome.

Adrenocortical Hyperfunction↗
PubMed2005

Myocardial disarray: an architectural disorganization linked with adrenergic stress?

BACKGROUND: Myocardial disarray is a structural abnormality found in specific zones of the normal heart. In some conditions, such as hypertrophic cardiomyopathy (HCM), its occurrence represents a pathological process leading to myocardial asynergy. The incidence of "pathological" myocardial disarray in humans is still not known. It has been suggested that a link exists between adrenergic overactivity and myocardial disarray. The aim of the present study is to compare heart findings in conditions with and without chronic sympathetic overtone for evidence of possible linkage in humans. MATERIALS AND METHODS: A total of 340 hearts were studied. They were divided into seven groups: sudden/unexpected coronary death; sudden/unexpected death in silent Chagas' disease; brain haemorrhage following berry aneurysm rupture; transplanted hearts; congestive heart failure, AIDS and cocaine abuse. Findings in these hearts were compared with anatomic changes in 92 control hearts, where the decedent had died from head trauma, electrocution, or carbon monoxide intoxication. The frequency and presence of myocardial disarray were recorded and correlated to heart weight, extent of myocardial fibrosis, and contraction band necrosis (CBN). RESULTS: Hearts from patients with conditions that increased sympathetic tone showed an association of myocardial disarray and contraction band necrosis without any relationship to heart weight. CONCLUSIONS: Myocardial disarray was observed in cardiac areas where it is not found normally. It was associated with adrenergic myocardial stress morphologically expressed by a higher number of foci (p<0.01) and myocells (p<0.001) with CBN versus findings in normal subjects. The condition deserves further study as a possible myocardial asynergic and arrhythmogenic factor especially in sudden/unexpected death.

Adrenocortical Hyperfunction↗
PubMed2004

Morphology of the pituitary gland in ferrets (Mustela putorius furo) with hyperadrenocorticism.

Pituitary tumours are the cause of hyperadrenocorticism in a variety of species, but the role of the pituitary gland in hyperadrenocorticism in ferrets is not known. In this species, the disease is mediated by the action of excess gonadotrophins on the adrenal cortex and is characterized by an excessive secretion of sex steroids. In this study, the pituitary gland of four healthy control ferrets, intact or neutered, and 10 neutered ferrets with hyperadrenocorticism was examined histologically following immunohistochemical labelling for adrenocorticotrophic hormone, alpha-melanocyte-stimulating hormone, growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin. Immunohistochemistry revealed that somatotrophs, thyrotrophs and lactotrophs were the most abundant cell types of the pars distalis of the pituitary gland in the healthy ferrets. The distribution of corticotrophs was similar to that in the dog and man. In ferrets, as in dogs, the melanotrophic cell was almost the only cell type of the pars intermedia. Gonadotrophs were found in the pars distalis of neutered, but not intact ferrets. All the ferrets with hyperadrenocorticism had unilateral or bilateral alterations of the adrenal gland. In addition, in the pituitary gland of two of these ferrets a tumour was detected. These tumours were not immunolabelled by antibodies against any of the pituitary hormones, and had characteristics of the clinically non-functional gonadotroph tumours seen in man. In some of the other ferrets low pituitary immunoreactivity for gonadotrophic hormones was detected, which may have been due to the feedback of autonomous steroid secretion by the neoplastic transformation of the adrenal cortex. It is concluded that initially high concentrations of gonadotrophins resulting from castration may initiate hyperactivity of the adrenal cortex. The low incidence of pituitary tumours and the low density of gonadotrophin-positive cells in non-affected pituitary tissue in this study suggest that persistent hyperadrenocorticism is not dependent on persistent gonadotrophic stimulation.

Adenoma↗
PubMed2006

Androgen excess in women--a health hazard?

A significant body of evidence suggests that androgens in women may play a role in the genesis of central adiposity and type 2 diabetes. There are two principal sources of circulating androgens in females: the ovary and the adrenal gland. In hyperandrogenic women, there are elevated serum concentrations of androstenedione and testosterone and, in up to 50% of the women, dehydroepiandrosterone sulfate (DHEAS). The androgen precursor DHEAS is of exclusive adrenal origin, suggesting that hyperandrogenic women have an elevated proportion of adrenal androgen production and secretion. Another cause of androgen excess in reproductive-age women is a decreased conversion of testosterone to estradiol by the aromatase enzyme complex. In this review, we will discuss the hypothesized clinical sequel of elevated androgens in women - an aspect of women's health highly neglected. Furthermore, an attempt is made to appreciate what causes the androgens to initially rise from normal levels, allowing the onset of pathophysiological processes towards diseases.

Adiposity↗
PubMed2006

The responses of growing pigs to a chronic-intermittent stress treatment.

Many of the stressor treatments used in animal models of depression have parallels in the normal experiences of domestic pigs. The experiment described here aimed to assess whether a chronic-intermittent stress regime caused behavioural or physiological changes, indicative of depression, in domestic pigs. Ten juvenile male pigs were exposed to a social and environmental stress regime. Over the stressor period, weight gain was significantly lower in test pigs than in control pigs. Stress treatment had a significant effect on salivary cortisol levels, with test pigs having a higher salivary cortisol concentration than control pigs after the stress treatment but not before. Test pigs showed less ventral lying than control pigs in the post-stress observation. A detrended fluctuation analysis (DFA) of postural behavioural organisation showed that test pigs had a more structured pattern of activity than controls in the post-stress observation and a tendency towards a more structured pattern in the pre-stress observation. There were no major behavioural differences between the two groups during three repeated open field tests. The results suggest that the stressor treatment did create a mild chronic stress, as indicated by the hypercortisolaemia and lower weight gain in the test pigs. However, no unambiguous behavioural indicators of depression were seen. The behavioural analysis did show that fractal techniques, such as DFA, could be applied to pig behaviour and that they can reveal extra novel information about the structure of an individual's behavioural organisation and how it changes in response to complex environmental stressors.

Adrenocortical Hyperfunction↗
PubMed2005

Evaluation of pressor sensitivity to norepinephrine infusion in dogs with iatrogenic hyperadrenocorticism. Pressor sensitivity in dogs with hyperadrenocorticism.

Hypertension is a common complication of canine hyperadrenocorticism. Increased pressor sensitivity to endogenous catecholamines is currently believed to be the main mechanism involved in the development of hypertension in human hyperadrenocorticism. The aim of this study was to evaluate pressor sensitivity to norepinephrine in dogs after induction of iatrogenic hyperadrenocorticism (I-HAC) by serial arterial blood pressure measurements during infusions of increasing dose rates of norepinephrine (0.1, 0.15, 0.2, 0.3, 0.4, 0.6, and 0.8 microg/kg/min) in eight dogs with I-HAC and eight control dogs. Systolic, diastolic, mean blood pressure and heart rate measurements were recorded. The changes in these parameters between the two groups of dogs were compared. Dogs in the I-HAC group had a more pronounced pressor response to norepinephrine infusions than control dogs since the infusions had to be stopped in seven of the dogs due to severe hypertension (>240 mmHg). The mean maximum tolerated dose rate in the control group was 0.6 microg/kg/min with a standard error of 0.0 and 0.34 microg/kg/min with a standard error of 0.08 in the I-HAC group. The study demonstrated the presence of increased pressor sensitivity to norepinephrine in dogs with I-HAC.

Adrenocortical Hyperfunction↗
PubMed2005

Effect of ACTH-induced hypercortisolemia on the EEG in patients with stress-related epilepsy.

PURPOSE: We assess the effect of acute hypercortisolemia induced by ACTH stimulation on seizures and EEG interictal spike activity in patients with localization-related epilepsy (LRE) and stress-related seizures. METHODS: Seven patients (3 males, 4 females) with LRE and stress-related seizures were studied. All patients underwent ACTH stimulation with 0.25-0.75 mg Cosyntropin intravenously at 8 am. Serum cortisol and ACTH levels were monitored half- to one-hourly for 4 to 6 hours. Video/EEG monitoring was also performed. RESULTS: ACTH injection induced hypercortisolemia in all patients. Hypercortisolemia was not associated with seizures or interictal spike facilitation in any patient. Two patients experienced seizures on the day of ACTH injection, one 8 hours after and another 15 and 12 hours after the injection, during a period when their cortisol levels had returned to normal. CONCLUSION: No reproducible interictal EEG changes occurred in any of the patients following ACTH injection.

Adolescent↗
PubMed1999

Corticosteroid-induced glaucoma attributable to an adrenocorticotropin-secreting malignant carcinoid tumor of the thymus.

PURPOSE: To describe the clinical and histopathologic findings in a patient with corticosteroid-induced open-angle glaucoma attributable to an adrenocorticotropin-secreting malignant carcinoid of the thymus. METHODS: Case report. In a 33-year-old man, the clinical course, laboratory findings, and imaging results as well as the histopathologic findings are described. RESULTS: Increased intraocular pressure in this patient represented a manifestation of severe hypercortisolism attributable to a malignant adrenocorticotropin-secreting carcinoid tumor. Surgical removal resulted in return of the intraocular pressure values to normal levels. CONCLUSION: Thymic carcinoid is a rare cause of Cushing syndrome, which can lead to increased intraocular pressure.

Adrenocortical Hyperfunction↗
PubMed1981

Surgical management of aldosterone-producing adrenal adenomas: a review of 16 patients.

Tabulation of the diagnostic evaluation and operative treatment of 16 patients with aldosterone-producing adrenal adenomas is presented. The diagnosis of primary aldosteronism was confirmed in all patients by biochemical and radiologic studies. Selective venous sampling of adrenal vein aldosterone localized the adenoma in 14 patients and proved to be the single most helpful diagnostic procedure. Computed tomography was used recently to confirm the localization of these interesting lesions and may become the initial noninvasive diagnostic study. Confidence in the accuracy of preoperative localization has led to the choice of the posterior approach to the involved adrenal gland. Postoperative morbidity has been low regardless of the operative approach; however, subjective patient acceptance of posterior adrenalectomy suggests a more comfortable convalescence and a more rapid return to normal activity.

Adenoma↗
PubMed2006

[Use of cabergoline in persisting Cushing's disease].

Cabergoline is a dopaminergic agonist with demonstrated efficiency of for the treatment of prolactin-secreting pituitary tumors. It has also been reported effective for patients with hypercortisolism uncontrolled by conventional therapies. We describe the use of cabergoline in three patients with Cushing's disease, one of them presenting a silent ACTH-secreting pituitary tumor. Those patients underwent surgery and only one has been treated with radiation therapy. However persisting hypercortisolism motivated the use of cabergoline. We describe a decrease or a normalization in hypercortisolism; for one of the subjects, tumor growth seemed to be stopped. While cabergoline can induce a suppression of cortisol secretion or a corticotroph tumor shrinkage, the sites of action remain unclear.

Adrenocortical Hyperfunction↗
PubMed2005

[What has changed in adrenalectomy? From open surgery to laparoscopy?].

INTRODUCTION: After the introduction of the laparoscopic approach in adrenal surgery, this technique has become the gold standard in surgical adrenal diseases. Nevertheless, comparative studies with open surgery are scarce and the impact of laparoscopic techniques on these diseases is unknown. OBJECTIVE: To evaluate our experience of adrenal surgery over a 14-year period, before and after the introduction of laparoscopic adrenalectomy, and to analyze the influence of this technique on the surgical management of adrenal diseases. PATIENTS AND METHOD: From January 1990 to June 2004, 78 patients underwent adrenalectomy. Between 1990 and 1998, open adrenalectomy was performed in 24 patients, while between 1999 and 2004, 54 patients underwent the laparoscopic approach and 1 underwent open surgery. Data for the open group were retrospectively reviewed while those for the laparoscopic group were prospectively registered in the advanced laparoscopic surgery database of Hospital Sant Pau (HSP). RESULTS: The mean age was 47 years (16-75) in the open group and was 49 years (17-77) (p = NS) in the laparoscopic group. Distribution by surgical indication was similar in both periods concerning primary hyperaldosteronism, hypercortisolism, and pheochromocytoma, with a significant increase in surgical cases indicated by malignancy (1 vs 4) or incidentaloma (2 vs 13) (p<.001). Operating time was reduced from 150 min (65-210) in the open group to 90 min (30-300) in the laparoscopic group (p<.01). Morbidity was also reduced (20% vs 6%, p<.01). The size of lesions resected by open or laparoscopic surgery (4 cm [0.4-16] vs 3.5 cm [1.2-14]) was similar. The mean length of hospital stay was reduced from 8 days (3-13) to 3 days (2-12) (p<.01). The number of adrenalectomies performed in HSP was 24 in the first period (1990-1997) vs 40 in the second (1998-2004). This represented an increase from 3/year to 6.6/year mainly due to the increase in the number of incidentalomas. CONCLUSIONS: The laparoscopic approach has improved immediate surgical results (operating time, morbidity, and length of hospital stay). There was a clear increase in the number of adrenalectomies, and especially of incidentalomas, due to improved diagnostic techniques and the availability of a less aggressive approach.

Adolescent↗