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Exacerbation of adjuvant arthritis by adrenalectomy is associated with reduced leukocyte lipocortin 1.

OBJECTIVE: Lipocortin 1 is a mediator of the antiinflammatory actions of therapeutic glucocorticoids. ENdogenous glucocorticoids modulate inflammatory arthritides including rheumatoid and adjuvant arthritis (AA), but the role of lipocortin 1 in this phenomenon is not known. We studied the effects of endogenous glucocorticoids on adjuvant arthritis and leukocyte lipocortin 1 content. METHODS: Adrenalectomy of sham adrenalectomy was performed 2 days before adjuvant injection in 170 g inbred Sprague-Dawley rats. Peripheral blood was obtained and disease severity assessed by delta paw volume and clinical score 14 days later. Leukocyte subset lipocortin 1 content was determined by double labeling permeabilization flow cytometry using specific monoclonal antibodies. RESULTS: Lipocortin 1 fluorescence was readily detected in control rat peripheral blood cells labeled with OX-1 (pan-leukocyte), OX-19 (CD5), W3/25 (CD4), and OX-8 (CD8). Lipocortin 1 fluorescence was significantly greater in polymorphonuclear leukocytes (PMN) (RP3; p < 0.01). Induction of AA was accompanied by significant increases in lipocortin 1 (p < 0.001) in all subsets. Sham adrenalectomy induced no significant change in AA rat leukocyte lipocortin 1. Adrenalectomy induced significant exacerbation of AA disease severity compared to sham operation (delta paw volume 1.43 +/- 0.1 vs 1.13 +/- 0 ml; p < 0.05). Adrenalectomy was also associated with significant reduction in lipocortin 1 content in all leukocyte subsets except PMN. Leukocyte lipocortin 1 content exhibited significant negative correlation with clinical disease severity (R2 = -0.55; p < 0.05). CONCLUSION: Endogenous glucocorticoids modulate leukocyte expression of lipocortin 1 in inflammatory disease, and reduced lipocortin 1 may be involved in the exacerbation of AA by adrenalectomy.

Adrenalectomy↗

[Laparoscopic adrenalectomy. A retrospective comparison with traditional methods].

BACKGROUND: After 3 years from the introduction of laparoscopic adrenalectomy in an endocrine surgery unit the results are retrospectively compared with those achieved by traditional techniques with the aim of comparing the respective advantages. METHODS: During this period 68 laparoscopic adrenalectomies have been performed. The main pre-, intra- e postoperative parameters of the adrenalectomies for benign neoplasm have been examined. Mean follow-up was 51 months (65.3 for open adrenalectomy and 18.8 for laparoscopic). RESULTS: Statistical studies were homogeneous between the two groups. The laparoscopic adrenalectomy--with the same effectiveness--thanks to less peritoneum and parietal stress, is followed by fewer postoperative complications, faster resumption of biological functions, earlier return to work and better cosmetic results. CONCLUSIONS: On the basis of our personal experience laparoscopic adrenalectomy is to be considered the treatment of choice in the majority of adrenal benign neoplasms.

Adrenalectomy↗

Adrenalectomy-induced granule cell degeneration in the rat hippocampal dentate gyrus: characterization of an in vivo model of controlled neuronal death.

The recent discovery that adrenalectomy results in hippocampal granule cell loss suggested that this phenomenon might be useful as a model of selective, experimentally controlled neuronal death possibly relevant to neurodegenerative disorders. This study was designed to provide a detailed qualitative anatomical description of the phenomenon and to determine whether adrenalectomy-induced dentate granule cell degeneration constitutes a reliable model of selective neuronal death. Silver impregnation staining revealed that granule cell degeneration begins immediately after adrenalectomy and continues for months in both sexes, in young and older adults, and in all strains tested. In one group of 77 adrenalectomized rats, 82% exhibited silver-impregnated granule cells. This phenomenon is extraordinarily selective in that no neurons other than dentate granule cells degenerated after adrenalectomy. There was considerable variability among animals in the number of cells degenerating at a given time-point or in the degree of ultimate cell loss. In the most extreme cases, virtually complete granule cell loss was present throughout approximately 80% of the dentate gyrus. Nissl staining revealed that degenerating granule cells exhibited coalescing of nuclear chromatin into multiple nuclear bodies and pyknosis without accompanying glial swelling. This morphology is distinct from the necrosis caused by other neurotoxic insults and is the subject of the ultrastructural companion paper identifying this type of cell death as apoptosis. Taken together, these results indicate that adrenalectomy reliably initiates an immediate, highly selective, and long-continuing process of hippocampal granule cell degeneration that exhibits morphological features characteristic of apoptosis, rather than necrosis. The possibility that this apoptotic cell death involves a biochemical cascade relevant to programmed cell death and/or neurodegenerative diseases suggests that this model may be valuable for studies of neuronal death and its prevention. Some practical guidelines for use of this model are described.

Adrenalectomy↗

Adrenalectomy and castration in the genetically obese (ob/ob) mouse.

The present studies have tested the hypothesis that adrenalectomy could modify the phenotypic expression of genetic obesity by examining the effects of adrenalectomy on the function of the gonadal system in lean and ob/ob mice. Corticosterone concentrations were undetectable in the adrenalectomized animals. Adrenalectomy significantly slowed the weight gain of obese mice in comparison to sham-adrenalectomized controls. Gonadectomy had no independent effect on weight gain. The testes, prostate, and seminal vesicles in the ob/ob mice were significantly smaller than in the lean animals. Castration lowered the weights of the prostate and seminal vesicles in the lean mice to weights close to those observed in the castrated ob/ob mice. Castration significantly increased the concentrations of LH and FSH in both ob/ob and lean mice, but the absolute concentrations were higher in the lean mice in both conditions. Adrenalectomy per se had no effect on the concentration of LH, FSH, or testosterone or on the weights of the prostate or seminal vesicles. These data indicate that adrenalectomy has no effect on the physiologic control of the reproductive system in genetically obese mice, and are consistent with the hypothesis that the defect in the ob/ob mouse is a modulator of steroid action which over expresses glucocorticoid effects and under expresses gonadal steroid effects.

Adrenal Glands↗

Adrenalectomy decreases corticotropin-releasing hormone gene expression and increases noradrenaline and dopamine extracellular levels in the rat lateral bed nucleus of the stria terminalis.

The bed nucleus of the stria terminalis (BNST) has a high density of corticotropin-releasing hormone (CRH)-containing neurons that are significantly innervated by noradrenergic and dopaminergic nerve terminals. This limbic structure is involved in the extrahypothalamic response to stress. The purpose of the present work is to study whether the absence of glucocorticoids, induced by a long-term adrenalectomy, regulates CRH gene expression and noradrenaline and dopamine extracellular levels in the rat BNST. The results showed that adrenalectomy decreases CRH mRNA in the dorsal lateral BNST but not in the ventral lateral BNST. Adrenalectomy also decreases CRH-like immunoreactivity both in BNST subnuclei and in the central nucleus of the amygdala. In addition, adrenalectomy significantly increases noradrenaline and dopamine extracellular levels in the lateral BNST. The present results suggest that adrenalectomy regulates CRH gene expression and noradrenaline and dopamine extracellular levels in the BNST in an opposite way. Thus, the present study adds novel evidence further supporting that the BNST and the central nucleus of the amygdala form part of an adrenal steroid-sensitive extrahypothalamic circuit that has been involved in fear and anxiety responses and in clinical syndromes such as melancholic depression, posttraumatic stress disorders, and addiction.

Adrenal Glands↗

Breast cancer: lack of prognostic value of adrenal pathology at adrenalectomy.

The adrenal glands of 58 patients undergoing adrenalectomy for advanced breast cancer were reviewed and correlated with subsequent course of the patients' disease. Three patients had thecomatous metaplasia in the adrenal cortex, six patients had myelolipomatous changes, and 13 patients had metastatic breast cancer in their adrenal glands at the time of adrenalectomy. Neither the presence of metastases nor myelolipomatous changes were associated with a long disease-free interval, a long period from mastectomy to adrenalectomy, or a prolonged postadrenalectomy survival. The patients with metastatic breast cancer in the adrenal glands had more widespread disease than patients without adrenal metastases. The presence of breast cancer metastases in the adrenal glands at the time adrenalectomy identifies patients further advanced in the course of their disease, but is not related prognostically to the effect of adrenalectomy.

Adrenal Gland Neoplasms↗

Results of endoscopic retroperitoneal adrenalectomy.

BACKGROUND: From March 1994 to August 1995 we performed extraperitoneal endoscopic adrenalectomy in 18 patients with adrenal gland tumors. METHODS: Two of these patients underwent bilateral adrenalectomy. For the extraperitoneal approach a pneumoretroperitoneum was established and three 10-mm trocars were inserted in the area of the conventional flank incision. Adrenalectomy was performed via these ports. Endoscopic retroperitoneal adrenalectomy was successful in 15 patients; three patients required a conventional operation via an extraperitoneal lumbar approach because of inadequate exposure of the adrenal gland. In patients with endoscopic retroperitoneal adrenalectomy median operative time amounted to 180 min (95-330). RESULTS: No postoperative complications were observed; median postoperative hospital stay was 5 days (3-12). CONCLUSIONS: The described approach produces rapid recovery and creates less postoperative pain.

Adrenal Gland Neoplasms↗

Inhibition of the adrenalectomy-induced increase in plasma renin concentration by vasoconstrictor agents in rats.

Plasma renin concentrations in rats increase after bilateral adrenalectomy without sodium substitution. The effects of i.v. infused (asp1-beta-amid, val5)-angiotensin II (1 mug/kg min), felypressin (phen2, lys8-vasopressin) (40 mU/kg min) and phenylephrine (30 mug/kg min) were investigated on the increase in plasma renin concentration. These effects of the agents were compared with their actions on blood pressure, heart rate and renal hemodynamics. In rats with destroyed macula densa cells the effect of bilateral adrenalectomy without sodium substitution was also studied. Adrenalectomy still increased the plasma renin concentration. Angiotensin II and felypressin, also depressed under these conditions the elevation of plasma renin concentration caused by adrenalectomy. The mechanism of the adrenalectomy-induced renin release and its suppression by vasoconstrictor agents is discussed.

Adrenalectomy↗

Adrenalectomy and chemical sympathectomy by 6-hydroxydopamine. Effects on basal and stimulated insulin secretion.

Influences of the sympatho-adrenal system on basal and stimulated insulin secretion were studied in vivo in the conscious mouse and rat. In the mouse, adrenalectomy or chemical sympathectomy, induced by 6-hydroxydopamine, lowered basal insulin concentrations moderately. A marked depression of basal insulin concentration (about 50%) was seen after the combined treatment of chemical sympathectomy and adrenalectomy. In short-term experiments in mice, insulin secretion stimulated by glucose or the cholinergic agonist carbachol was enhanced after chemical sympathectomy and/or adrenalectomy, whereas insulin release induced by the synthetic octapeptide of cholecystokinin (CCK-8) was inhibited. The promoting influences on the insulin secretory response to carbachol displayed a rapid development whereas those to glucose developed more slowly. In contrast, the inhibiting effect on CCK-8 stimulated insulin release vanished with time. The insulin secretory response to the beta 2-adrenoceptor stimulator, terbutaline, was increased after chemical sympathectomy, unaffected by adrenalectomy, and decreased after chemical sympathectomy plus adrenalectomy. The glucose elimination rate after 6 weeks of chemical sympathectomy was increased in mice and decreased in rats. The insulin secretory response to glucose was enhanced in mice, whereas it tended to diminish in rats after long-term sympathectomy. In conclusion, the sympatho-adrenal system is involved in regulation of basal insulin concentrations in the mouse, and apparently is of great importance for stimulated insulin secretion; the influence being dependent on the nature of the secretagogue.

Adrenalectomy↗

Effect of ACTH, adrenalectomy and the combination treatment on the density of 5-HT2 receptor binding sites in neocortex of rat forebrain and 5-HT2 receptor-mediated wet-dog shake behaviors.

The effect of ACTH and/or adrenalectomy on serotonin (5-HT)2 receptor binding sites was evaluated in the neocortex of rat forebrain. One day after the adrenalectomy or sham operation, ACTH (50 micrograms/day) was injected subcutaneously into adult male SD rats for 10 consecutive days. Saturation analysis showed that subchronic ACTH treatment significantly increased the Bmax values for 3H-ketanserin binding without any change in the Kd values. Moreover, this ACTH-induced increase in the Bmax values was prevented by adrenalectomy. The concentrations of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) measured by HPLC-ECD were not altered by these manipulations. Ten-day administration of corticosterone (20 and 50 mg/kg) also increased 5-HT2 receptor density in the neocortex of rat forebrain. 5-HT2 (and 5-HT1C) receptor agonist, (+/-)DOI-induced wet-dog shakes in ACTH and/or adrenalectomy-treated rats were also examined. Ten-day administration of ACTH enhanced (+/-)DOI-induced wet-dog shakes and this increase was prevented by adrenalectomy. These results indicate that subchronic adrenocorticotropin-adrenal axis activation of rats increases both the number of 5-HT2 receptors in neocortex of forebrain and the wet-dog shake responses induced by (+/-)DOI.

Adrenalectomy↗

[Hyperaldosteronism persisting after subtotal adrenalectomy].

BACKGROUND: Primary aldosteronism is known to be caused by aldosterone-producing adenoma (APA). Total adrenalectomy is the standard procedure. In contrast to bilateral adrenal diseases (e.g., MEN II pheochromocytomas), there is no consensus about the effect of subtotal adrenalectomy. CASE REPORT: A 44-year-old patient with primary aldosteronism caused by APA underwent subtotal adrenalectomy including removal of one adenoma. Because hypertension and hypokalemia did not disappear and hyperaldosteronism persisted, the patient had to undergo reoperation in which the adrenalectomy was completed. DISCUSSION: Subtotal adrenalectomy in patients with Conn's syndrome is an interesting therapeutic option,whereas its effect is much higher in hereditary diseases of the adrenal gland. The benefit of preserved adrenal tissue has to be weighed against a possible persistence of hyperaldosteronism, especially in cases with normal opposite adrenal glands.

Adrenal Cortex Neoplasms↗

[The choice between transperitoneal and retroperitoneal adrenalectomy. A prospective study].

INTRODUCTION: The aim of this prospective study was to evaluate the optimal surgical approach to endoscopic adrenalectomy. PATIENTS AND METHODS: Between March 1997 and February 2003, we performed 221 endoscopic adrenalectomies in 202 patients (right side 83, left side 100, bilateral 19), with an conversion rate of 2,5%. In 197 patients endoscopic adrenalectomy was carried out via retropertioneal approach 128 times and via transperitoneal approach 88 times. RESULTS: Endoscopic adrenalectomy was performed in 98% of the total number patients. No statistically significant influence ( P=0.05) was found for the parameters intraoperative blood loss, rate of postoperative complications, or duration of hospitalization in regard to the procedure. The operative time and learning curve were significantly longer with the retroperitoneal approach. Multivariate analysis identified surgical approach, tumor size (5 cm), and body mass index (25) as independent factors for operative time. CONCLUSION: The lateral transperitoneal approach is the optimal procedure for endoscopic adrenalectomy.

Adrenal Gland Neoplasms↗

Laparoscopic adrenalectomy for pheochromocytoma.

aparoscopic adrenalectomy is the standard for most surgical adrenal diseases. The aim of this study was to evaluate the safety and effectiveness of laparoscopic adrenalectomy for patients with pheochromocytoma. The medical records of 39 consecutive patients who underwent laparoscopic adrenalectomy for pheochromocytomas from 1994 to 2000 at the University of California-San Francisco were reviewed. Three groups of patients were identified. The first group comprised 17 patients with classic symptoms and signs of pheochromocytoma. The second group comprised 17 patients who had minimal symptoms and incidentally discovered pheochromocytoma (i.e., "incidentaloma"), almost half of whom inappropriately underwent fine-needle biopsies before diagnosis. The third group consisted of 5 patients who had acute hypertensive crises and required intensive preoperative preparation. The mean age of the 22 men and 17 women was 46 years (range 20-84 years), and the mean adrenal tumor size was 4.8 cm (range 2-12 cm). A total of 43 laparoscopic adrenalectomies were performed for 35 patients with unilateral tumors and 4 patients with bilateral tumors. The retroperitoneal approach was used in four patients and the lateral transabdominal approach in the remaining patients without conversion to an open operation. There were no intraoperative complications or mortality. The mean duration of hospitalization was 1.7 days. In conclusion, patients with pheochromocytoma have a wide spectrum of presentations, from minimal symptoms to hypertensive crises. When evaluating an incidentaloma, pheochromocytoma should be excluded by metabolic testing, not by needle biopsy. Laparoscopic adrenalectomy is the preferred surgical approach for patients with pheochromocytoma because it is safe and efficacious.

Adrenal Gland Neoplasms↗

Study of three patients with congenital adrenal hyperplasia treated by bilateral adrenalectomy.

Medical management of congenital adrenal hyperplasia (CAH) patients has led to suboptimal results in most cases. High glucocorticoid doses, often needed to suppress adrenal androgen production, may lead to signs of Cushing syndrome. Incompletely suppressed androgen levels commonly lead to premature closure of growth centers, acne, virilization, precocious puberty, irregular or absent menses, and decreased fertility in female CAH patients. A newly proposed therapy for CAH patients is bilateral adrenalectomy. Three Caucasian female patients with 21-hydroxylase deficiency were treated with bilateral adrenalectomy. Two of the three procedures were accomplished laparoscopically. In each patient, medical management alone was unsuccessful. Two patients had salt-losing 21-hydroxylase deficiency. The third patient had uncontrolled hyperandrogenism complicated by obesity and glucose intolerance. All patients had low height percentiles with respect to their normalized percentiles for weight. Bone age was advanced in one patient. Androgen and renin levels were well controlled in two patients, whereas the third patient had persistent hyperandrogenism. Bilateral adrenalectomy was performed at the ages of 14, 19, and 30 years with follow-up, to date, of 25 months, 10 months, and 26 months, respectively. Postoperatively, all patients were free from hyperandrogenism. One patient experienced one episode of urosepsis precipitating an addisonian crisis. Bilateral adrenalectomy may successfully address the problems of increasing steroid requirements and hyperandrogenism in patients with severe CAH. The ability to perform this operation laparoscopically coupled with the overall metabolic benefits make bilateral adrenalectomy a reasonable alternative to lifelong androgen suppression in select patients.

Adrenal Hyperplasia, Congenital↗

Long-term results of total adrenalectomy for Cushing's disease.

The objective of this study was to present the long-term results of total adrenalectomy for Cushing's disease. Forty-four patients undergoing total adrenalectomy for Cushing's disease between 1953 and 1989 at Leiden University Medical Center, The Netherlands, were studied retrospectively. Remission was achieved in 42 patients (95%), with a mean duration of 19 years. Adrenal remnants were observed in 12 patients (27%), and were without clinical consequence in the majority of patients, but caused early recurrent disease in 2 patients. Nine patients (20%) experienced Addisonian crises up to 30 years following treatment. Nelson's syndrome developed in 10 patients (23%) 7-24 years following total adrenalectomy. Prior pituitary irradiation was a protective factor against Nelson's syndrome as it delayed its onset (p = 0.025). On the other hand, subnormal dose or noncontinuous glucocorticoid replacement therapy was associated with increased risk of development of Nelson's syndrome (p = 0.047). The incidence of Nelson's syndrome increased with prolonged follow-up, and female patients seemed to be at increased risk. Quality-of-life assessment showed less favorable scores on mental health and health perception scales, for which no explanation can be found except the long-lasting metabolic effects of Cushing's disease, even when successfully treated. In conclusion, total adrenalectomy remains the final treatment for Cushing's disease. The presence of adrenal remnants which can cause recurrent disease and the development of Nelson's syndrome during prolonged follow-up enhance the need for continued regular follow-up. Pituitary irradiation prior to total adrenalectomy delays the onset of Nelson's syndrome.

Addison Disease↗

Comparison of the hemodynamic parameters of open and laparoscopic adrenalectomy for pheochromocytoma.

Laparoscopic adrenalectomy has gained widespread popularity for treating a variety of adrenal disorders including pheochromocytoma, but the effects of pneumoperitoneum on the hemodynamics of patients with catecholamine-secreting tumors are poorly understood. The goal of this study was to compare the effects of carbon dioxide pneumoperitoneum and tumor manipulation on the hemodynamic parameters in two groups of patients with sporadic pheochromocytomas less than 7 cm in size. Group 1 patients (n = 11) underwent lateral transabdominal laparoscopic adrenalectomy, and group 2 (n = 11) underwent adrenalectomy by the open anterior approach. The mean follow-up was 37 months in group 1 (range 26-51 months) and 52 months in group 2 (range 27-72 months). All patients undergoing laparoscopic adrenalectomy experienced intraoperative hypertension (blood pressure > or = 200/90 mmHg), as did 73% with the open approach, but the difference was not significantly different. Intraoperative hypotension (systolic blood pressure < 80 mmHg) occurred in four group 1 patients compared to six patients in group 2. Mean arterial pressure, central venous pressure, and pulmonary capillary wedge pressure were significantly higher in group 1 patients prior to tumor excision, but there was no difference in pulse, cardiac index, or left ventricle work index at any point during the procedure. There were no conversions or complications in the laparoscopic group; one patient in group 2 developed an incisional hernia. Although laparoscopic adrenalectomy for pheochromocytoma is associated with a greater increase in mean arterial pressure, central venous pressure, and pulmonary capillary wedge pressure, the creation of pneumoperitoneum does not significantly change the cardiac index or left ventricle work index. Carbon dioxide pneumoperitoneum is well tolerated in patients with pheochromocytoma.

Adrenal Gland Neoplasms↗

Technique and results of laparoscopic adrenalectomy.

The aim of this report is to evaluate the benefits of laparoscopic adrenalectomy in terms of perioperative morbidity, complications and patients recuperation. We reviewed our experience with laparoscopic adrenalectomy in 47 consecutive patients who underwent adrenalectomy over a 4-year period. We used the lateral transperitoneal approach in all cases. The indications for adrenalectomy were Conn's adenoma in 24 patients, pheochromocytoma in 11, Cushing's syndrome in 3 and incidental adrenal tumour in 9. The average duration of surgery was 130 min (range, 60-300 min) and average adrenal gland size was 3.4 cm (range, 1.2-8 cm). Conversion from laparoscopy to laparotomy was necessary in three patients (6.4%), and postoperative complications occurred in two patients. There was no mortality. Laparoscopic adrenalectomy can be considered the method of choice for managing almost all adrenal masses, because of its low morbidity and short postoperative recovery. The main difficulty is to identify the adrenal gland, so several technical procedures are suggested.

Adrenal Gland Neoplasms↗

The positive impact of laparoscopic adrenalectomy on complications of adrenal surgery.

BACKGROUND: This study was conducted to determine whether laparoscopic adrenalectomy (LA) has had a positive impact on the incidence and nature of adrenalectomy-related complications, as compared with the prelaparoscopic era. METHODS: All English language reports of patients undergoing either open adrenalectomy (OA) or LA from 1980 to 2000 were identified by Medline search. Reports were analyzed for the frequency and type of complications, with a minimum of 10 cases or studies required for inclusion. Complications were stratified by type and/or organ system involved, and groups were compared statistically using generalized linear model methods. RESULTS: Complications were tabulated from 50 studies of LA involving 1,522 patients and 48 studies of OA comprising 2,273 patients. Among the reports, 22 compared LA and OA within a single institution. The total reported complication rate was 25.2% with LA versus 10.9% with OA (p < or = 0.0001). The incidence of bleeding complications was higher with LA (4.7%) than OA (3.7%) (p < or = 0.0001). As compared with LA, OA had a significantly higher incidence of associated organ injury (2.4% vs 0.7%), mainly to the spleen, and more wound (6.9% vs 1.4%), pulmonary (5.5% vs 0.9%), cardiac (1.6% vs 0.3%), and infectious (5.8% vs 1.6%) complications (p < or = 0.0001). No significant differences in gastrointestinal, thromboembolic, or neurologic complications were seen. The mortality rate was 0.3% after LA and 0.9% after OA. The difference was not significant. CONCLUSIONS: Laparoscopic adrenalectomy has resulted in fewer adrenalectomy-related complications than seen historically with OA. Fewer wound and pulmonary complications and a reduced incidence of incidental splenectomy are primarily responsible for this improved outcome.

Adrenal Glands↗