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Early ("prophylactic") oophorectomy and adrenalectomy in carcinoma of the breast: a ten-year follow-up.

Early "prophylactic" oophorectomy and adrenalectomy has been performed on 12 patients with carcinoma of the breast. The patients selected were considered to have a very bad prognosis on account of axillary node involvement associated with internal mammary chain deposits (9 patients), supraclavicular nodes (2 patients) and a parasternal mass (1 patient). Five patients had evidence of spread beyond the primary lymph drainage area (axillary and internal mammary nodes), and all had died within 4 years. In 7 patients the disease was confined to the primary lymph drainage area and 4 lived for more than 10 years, 3 being alive and well at 11 to 12 years. This is a higher proportion than in a control series but does not quite reach the level of statistical significance. In the 7 patients with disease confined to the axillary and internal mammary nodes prognosis was not apparently related to malignancy determined histologically, but did have an association with the extent of invasion of the axillary nodes. Urinary oestrogen estimations performed in 4 patients did not give any evidence that outcome was related to persistence of oestrogen production. Details of the patients' management and replacement therapy are given and from prolonged personal follow-up of these patients it is concluded that women who have undergone oophorectomy and adrenalectomy are able to lead full and active lives.

Adrenalectomy↗

A study of the glycerol phosphate acyltransferase and dihydroxyacetone phosphate acyltransferase activities in rat liver mitochondrial and microsomal fractions. Relative distribution in parenchymal and non-parenchymal cells, effects of N-ethylmaleimide, palmitoyl-coenzyme A concentration, starvation, adrenalectomy and anti-insulin serum treatment.

1. GPAT (glycerol phosphate acyltransferase) and DHAPAT (dihydroxyacetone phosphate acyltransferase) activities were measured both in subcellular fractions prepared from fed rat liver and in whole homogenates prepared from freeze-stopped pieces of liver. 2. GPAT activity in mitochondria differed from the microsomal activity in that it was insensitive to N-ethylmaleimide, had a higher affinity towards the palmitoyl-CoA substrate and showed a different response to changes in hormonal and dietary status. 3. Starvation (48 h) significantly decreased mitochondrial GPAT activity. The ratio of mitochondrial to microsomal activities was also significantly decreased. The microsomal activity was unaffected by starvation, except after adrenalectomy, when it was significantly decreased. Mitochondrial GPAT activity was decreased by adrenalectomy in both fed and starved animals. 4. Acute administration of anti-insulin serum significantly decreased mitochondrial GPAT activity after 60 min without affecting the microsomal activity. 5. A new assay is described for DHAPAT. The subcellular distribution of this enzyme differed from that of GPAT. The highest specific activity of DHAPAT was found in a 23 000 gav. pellet obtained by centrifugation of a post-mitochondrial supernatant. This fraction also contained the highest specific activity of the peroxisomal marker uricase. DHAPAT activity in mitochondrial fractions or in the 23 000 gav. pellet was stimulated by N-ethylmaleimide, whereas that in microsomal fractions was slightly inhibited by this reagent. The GPAT and DHAPAT activities in mitochondrial fractions had a considerably higher affinity for the palmitoyl-CoA substrate. 6. Total liver DHAPAT activity was significantly decreased by starvation (48 h), but was unaffected by administration of anti-insulin serum. 7. The specific activities of GPAT and DHAPAT were lower in non-parenchymal cells compared with parenchymal cells, but the GPAT/DHAPAT ratio was 5--6-fold higher in the parenchymal cells.

Acyltransferases↗

Adipocyte G-proteins and adenylate cyclase. Effects of adrenalectomy.

Steroid hormones modulate the ability of cells to respond to hormones that act via cyclic AMP. In adipocytes of adrenalectomized rats, cyclic AMP accumulation and lipolysis in response to adrenaline are attenuated. However, the mechanism(s) of these effects are poorly understood. The effects of altered glucocorticoid status in vivo on the steady-state amounts of components of the hormone-sensitive adenylate cyclase were analysed in rat adipocytes. beta-Adrenergic receptors were analysed by using radioligand binding and immunoblotting with an anti-receptor antiserum. Neither the amount of radioligand binding nor the amount of beta-adrenergic-receptor peptide (Mr 67,000) was altered by adrenalectomy, whereas treatment of adrenalectomized rats with dexamethasone was found to increase both parameters by more than 25% with respect to the control. Forskolin-stimulated adenylated cyclase activity was unchanged in membranes isolated from adipocytes of adrenalectomized rats, but was decreased (50%) in those from dexamethasone-treated rats. The alpha-subunit of Gs was probed by using cholera-toxin-catalysed ADP-ribosylation. Immunoblotting was used to analyse the steady-state amounts of G-protein beta-subunits (beta-G35/36). Adrenalectomy was associated with decreases in the steady-state amounts of alpha-Gs (30%) and beta-G35/36 (50%). Dexamethasone treatment of adrenalectomized animals partially restored the lipolytic response of adipocytes to adrenaline and the amounts of alpha-Gs, increased the amounts of beta-G35/36 subunits from 50% to 150% of control values, increased beta-adrenergic receptors by more than 25% and decreased adenylate cyclase activity (50%). These results suggest that the steady-state amounts of components of hormone-sensitive adenylate cyclase are differentially regulated by glucocorticoids.

Adenylyl Cyclases↗

Changes in cardiac and hepatic glucocorticoid receptors after adrenalectomy.

1. The total number of specific dexamethasone-binding sites in rat heart and liver cytosol was measured at intervals after adrenalectomy. 2. Between 12 and 48 h after adrenalectomy there was a significant increase in the number of binding sites in both heart and liver cytosol. Affinity was unchanged. 3. Of the [3H]corticosterone bound to liver cytosol proteins after an intravenous injection 98% disappeared within 2 h in vivo. Dissociation of endogenous corticosterone-receptor complexes in liver cytol will thus be substantially complete some hours before the number of receptors increases. 4. It was concluded that there is a true increase in the number of glucocorticoid receptors occurring principally between 12 and 48 h after suppression of endogenous steroids.

Adrenalectomy↗

Adrenalectomy and glucocorticoid administration in vivo do not affect production of 6-oxoprostaglandin F1 alpha by rat aortae.

1. Rats were bilaterally adrenalectomized and treated for periods of up to 32 days with doses of dexamethasone equivalent to physiological and supraphysiological endogenous glucocorticoid secretion. Aortic production of 6-oxoprostaglandin F1 alpha (6-oxo-PGF1 alpha) was measured by radioimmunoassay of the supernatant fluid from rings of aorta incubated in vitro. 2. Up to 32 days after adrenalectomy, neither adrenalectomy nor dexamethasone (2 micrograms/day and 20 micrograms/day) influenced aortic 6-oxo-PGF1 alpha production. 3. High doses of dexamethasone (60 micrograms/day for 6 days) in the presence or absence of mineralocorticoid (11-deoxycorticosterone, 600 micrograms/day) had no effect on aortic 6-oxo-PGF1 alpha production. 4. In contrast to the lack of effect of dexamethasone administered in vivo, incubation of aortic discs for 5 h with dexamethasone (1 mumol/l) in vitro caused inhibition of aortic 6-oxo-PGF1 alpha production to 23% of control levels. 5. Alteration in endogenous glucocorticoid secretion is unlikely to be involved in the physiological regulation of aortic 6-oxo-PGF1 alpha production.

6-Ketoprostaglandin F1 alpha↗

11 beta-hydroxylase deficiency: management of a difficult case by laparoscopic bilateral adrenalectomy.

A 14-year-old girl presented with short stature and progressive virilization. She had not undergone the menarche. On investigation, she had elevated testosterone, androstenedione, dihydroepiandrosterone sulphate and 17 alpha-hydroxyprogesterone levels, which were all suppressed by overnight dexamethasone to within their normal ranges. An initial diagnosis of 21-hydroxylase deficiency was revised to 11 beta-hydroxylase deficiency after a tetracosactrin stimulation test, which showed only a modest rise in 17 alpha-hydroxyprogesterone level (from 92 nmol/l at baseline to 133 nmol/l at 60 minutes) and measurement of the basal 11-deoxycortisol, which was grossly elevated. Treatment with dexamethasone 0.5 mg nocte resulted in suppression of androgens in the daytime, but not in the evening, particularly androstenedione. Treatment with hydrocortisone 10 mg b.d. failed to suppress testosterone or androstenedione over a 24-hour period. Addition of cyproterone and oestrogen supplements had no effect and significant virilization persisted. Laparoscopic bilateral adrenalectomy was therefore performed as definitive treatment and resulted in remarkable clinical and biochemical improvement. This case illustrates difficulties in correct diagnosis, choice of appropriate steroid regimen and monitoring efficacy of treatment in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. More aggressive management with earlier bilateral adrenalectomy may be appropriate in selected cases.

Adolescent↗

Long-term adrenalectomy can decrease or increase hippocampal dentate gyrus volumes.

Male and female Long-Evans adult rats were adrenalectomized and sacrificed 6 weeks later to determine whether dentate gyrus damage would differ in females and males. A subset of adrenalectomized rats of both sexes had significantly reduced dentate gyrus volumes compared to the same sex SHAM operated rats. The remainder of the male and female adrenalectomized rats which did not have clear dentate gyrus damage had significantly larger dentate gyrus volumes compared to the same sex SHAM rats. The dentate gyrus volumes of all adrenalectomized rats were significantly correlated with two indices of residual hormonal levels (Na+/K+ ratios and body weight gain 6 weeks after surgery), indicating that endogenous corticosterone levels may be a determining factor in the response of the dentate gyrus to adrenalectomy. These dentate gyrus volumetric changes could not be attributed to tissue shrinkage as there were no changes in CA3 volumes in any of the groups. These results suggest that long-term adrenalectomy can result in either increased or decreased dentate gyrus volumes and that the adrenal steroid levels of each individual adrenalectomized rat may be the factor determining the direction of the dentate gyrus volumetric response.

Adrenal Glands↗

Effect of corticosterone and adrenalectomy on NMDA-induced cholinergic cell death in rat magnocellular nucleus basalis.

The present study demonstrates the effects of adrenalectomy and subcutaneously administered corticosterone on N-methyl-D-aspartate-induced neurodegeneration in the cholinergic magnocellular basal nucleus of the rat. NMDA was unilaterally injected into the nucleus basalis at different plasma corticosterone concentrations in adrenalectomized rats, in adrenalectomized animals with subcutaneously implanted cholesterol-corticosterone pellets containing 25% or 100% corticosterone, and in sham-adrenalectomized controls. The neurotoxic impact of the NMDA injection in the various experimental groups was assessed by the loss of cholinergic fibers stained with acetylcholinesterase histochemistry in the parietal neocortex. Reactive cortical astrocytes as a result of the treatments were detected by glial fibrillary acidic protein immunohistochemistry. Measurements of the densities of astrocytes and cholinergic fibers at the injected side of the brain were carried out by image analysis. Adrenalectomy significantly potentiated the NMDA-induced neurodegeneration by 50%, while chronic administration of corticosterone significantly attenuated the NMDA-neurotoxicity in a dose-dependent manner. Compared to the ADX group, 25% corticosterone application reduced the NMDA damage by 37%, whereas the 100% corticosterone pellet diminished NMDA neurotoxicity by 75%. Both ADX and ADX + corticosterone implantation enhanced the NMDA-induced GFAP immunoreactivity. The increase of GFAP immunoreactivity was most pronounced in the adrenalectomized rats supplied with the 100% corticosterone pellets. The results demonstrate that corticosterone exerts a potent neuroprotective effect on NMDA-induced neurotoxicity in the magnocellular nucleus basalis. The activated astroglia suggest that astrocytes may contribute to the beneficial effect of corticosterone in the neuroprotective mechanisms against excitotoxic neuronal injury.

Acetylcholinesterase↗

Corticotropin-releasing factor but not urocortin is involved in adrenalectomy-induced adrenocorticotropin release.

Urocortin, a new corticotropin-releasing factor (CRF)-related peptide, has been reported to have the ability to bind to CRF receptors and to stimulate adrenocorticotropin (ACTH) secretion from the rat anterior pituitary in vivo and in vitro. In this study, we examined the effect of intravenous administration of urocortin-antiserum to investigate the role of endogenous urocortin on ACTH secretion from rat anterior pituitary after adrenalectomy. Male Sprague-Dawley rats, which were maintained in a conscious and undisturbed condition, were administered non-immunized rabbit serum (NRS), CRF-antiserum or urocortin-antiserum at a volume of 1 ml/kg b.w. 15 min before the injection of secretagogues. Synthetic rat urocortin (2 microg/kg B.W.) increased plasma ACTH concentrations by about sixfold the basal concentration. The pretreatment with urocortin-antiserum but not CRF-antiserum abolished the urocortin-induced increase in plasma ACTH concentrations. In adrenalectomized rats, plasma ACTH concentrations were markedly increased at basal conditions, and rapidly reduced after the administration of CRF-antiserum. By contrast, administration of urocortin-antiserum did not alter ACTH secretion induced by adrenalectomy. Our results suggest that endogenous urocortin is unlikely to be involved in ACTH release in adrenalectomized rats.

Adrenalectomy↗

Simultaneous bilateral laparoscopic adrenalectomy in ACTH-independent macronodular adrenal hyperplasia.

Laparoscopic surgery for urological conditions has now become popular worldwide. The case is reported of a 56-year-old woman who underwent simultaneous bilateral laparoscopic adrenalectomy for adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasia (AIMAH), followed by autotransplantation of resected adrenal gland fragments. Simultaneous laparoscopic adrenalectomies seem feasible for a patient with AIMAH because of its minimally invasive nature. However, autotransplantation of adrenal fragments failed in this patient with AIMAH.

Adrenal Cortex↗

Laparoscopic adrenalectomy: a 6-year experience of 59 cases.

BACKGROUND: The aims of this paper were to review our experience with laparoscopic transperitoneal adrenalectomy, report on outcomes in comparison with the published literature, and demonstrate any learning curve with the technique. METHODS: A review of our database and patient records was carried out for the period April 1995 to December 2000. Patient demographics, tumour characteristics, operating times, outcomes and lengths of stay were studied. Diagnostic tools, including a comparison between tumour size on computed tomography scanning and on pathological section were reviewed. A comprehensive literature review was conducted using MEDLINE. RESULTS: Indications for surgery included 33 patients with primary hyperaldosteronism (29 adenomas, 4 hyperplasias), 12 phaeochromo-cytomas, 7 cortisol-secreting adenomas, 4 non-secreting adenomas, 1 medullary cyst, 1 metastasis and 1 ganglioneuroma. The tumours ranged in size from 7 to 110 mm. All tumours were localized and lateralized preoperatively using standard techniques. Throughout the review period, six open procedures were undertaken electively, for various reasons. Three cases were converted to open procedures (5.1%). Thirty-eight left and 21 right procedures were undertaken. For all laparoscopic procedures, the average time in the operating theatre was 175.1 min. Men took 188.3 min compared with 165.7 min for women. Left-sided lesions took 178.72 min compared with 167.63 min for right-sided lesions. The average length of stay was 3.8 days. There was one wound infection, one blood transfusion and two readmissions: one for pain control in a patient with difficult home circumstances, and one patient suffered transient hypoadrenalism. CONCLUSION: The results achieved in our initial experience with this technique are comparable with the published literature. The results confirm that laparoscopic adrenalectomy is the method of choice for resection of benign adrenal pathology. The procedure has a learning curve and should be performed by a surgeon experienced in both open and laparoscopic adrenal surgery.

Adrenal Gland Diseases↗

Adrenalectomy increases neurogenesis but not PSA-NCAM expression in aged dentate gyrus.

Ageing is accompanied by a decline in neurogenesis and in polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) expression within the hippocampus and by elevated basal levels of circulating corticosterone. In a companion study, we demonstrated that suppression of corticosterone by adrenalectomy increased neurogenesis and PSA-NCAM expression in the dentate gyrus of adult rats. Here we show that adrenalectomy increased neurogenesis in this structure in old rats, as measured by the incorporation of 5-bromo-2'-deoxyuridine in neuronal progenitors. This effect was prevented by corticosterone replacement. In contrast, PSA-NCAM expression remained unchanged in comparison with controls. Thus, in the aged brain, stem cells are still present and able to enter the cell cycle. This may point to ways of protecting or treating age-related cognitive impairments.

Adrenal Glands↗

Changes in urinary output during laparoscopic adrenalectomy.

OBJECTIVE: To better understand the physiological effects of pneumoperitoneum, by examining changes in urinary output during gaseous and gasless laparoscopic adrenalectomy. PATIENTS AND METHODS: Laparoscopic adrenalectomy was performed with gas in six patients and without in three. Urinary output was measured during insufflation and after desufflation. RESULTS: In all patients who received gas, the urinary output was significantly decreased during insufflation and significantly increased after desufflation. However, there were no changes in urinary output in patients who did not receive gas. CONCLUSION: For the safety of laparoscopic surgery it is important to recognise that oliguria occurs during pneumoperitoneum, although the changes in urinary output caused no complications in renal function.

Adrenalectomy↗

Diagnosis of pheochromocytoma and laparoscopic adrenalectomy in two anephric patients with von Hippel-Lindau disease.

This study reports the first two cases of laparoscopic treatment of functional pheochromocytomas in patients with von Hippel-Lindau (VHL) disease receiving regular dialysis treatment. The genetic changes predisposing to pheochromocytoma, diagnostic procedures, and surgical management were analyzed. Both patients were considered at low risk of developing pheochromocytoma because they belonged to VHL families with 10 and 25 affected relatives without pheochromocytoma (VHL type 1 families). The mutation responsible for the disease was a stop codon in one case and a missense change in the other. Multiple renal cell carcinomas had required removal of the kidneys at age 37 in one patient and age 25 in the other patient. Computed tomography scan was crucial for diagnosis, showing a unilateral enlarged adrenal gland after 3 and 6 years on regular dialysis. No change in blood pressure was observed. MIBG scintigraphy was negative. Plasma epinephrine in one case and dopamine in the other were increased compared with patients on hemodialysis without pheochromocytoma. Pheochromocytomas were removed successfully by laparoscopic adrenalectomy. Lifelong follow-up of all affected tissues is required in all VHL patients, and pheochromocytoma should be screened for even in the absence of family history in large kindreds. Computed tomography scan allows early recognition, and patients on hemodialysis are responsive to laparoscopic adrenalectomy.

Adrenal Gland Neoplasms↗

Time course of the effects of steroid hormone deprivation elicited by ovariectomy or ovariectomy plus adrenalectomy on the affinity and density of GABA binding sites in distinct rat brain areas.

The time course of the behaviour of GABAA receptors (affinity of muscimol for GABA binding sites and their number) in membranes obtained from five distinct rat brain areas was evaluated in dependence of the decline of the serum concentrations of estradiol and progesterone following hormone deprivation by either ovariectomy (OVX) or ovary- plus adrenalectomy (OVX-ADX) after 1, 2, 3, 5, 14 and 30 days. Diestrus rats served as control. The effect of OVX on the GABA binding sites was due to a decrease of affinity rather than alterations in their density. Conversely, the combined surgery of OVX plus ADX affected both the affinity and the density. Also, the OVX-linked changes of muscimol binding were observed only after five days as compared to control animals, while the initial OVX-ADX associated changes occurred already after one day. OVX-ADX produced significant decreases in the number of binding sites at the shortest times investigated, in frontal cortex (FC) at day one and two and in the medulla oblongata (MED) after three days, which disappeared in the subsequent times studied. Concomitant with the major decrease of steroid hormone serum levels one day after OVX-ADX the FC displayed an increase in affinity by 45%. From the time when steroid serum levels are low the alterations in affinity elicited by both OVX-ADX and OVX only take a similar course, reflected by the following decrease in affinity. In MED an additional adrenalectomy did not significantly modify the OVX linked decrease of affinity, except that the initial effect was already evident two days after OVX-ADX.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

[Postoperative polyuria after laparoscopic adrenalectomy for pheochromocytoma].

Disturbances of osmoregulation leading to polyuria are well known complications after operations in the sella region. In contrast, increased urinary output following adrenalectomy is rare. We report a case of postoperative polyuria after laparoscopic adrenalectomy for pheochromocytoma with urine output up to 15 l per day. Treatment included careful monitoring of the patient and intravenous and oral replacement of fluids and electrolytes. In our case a normalisation of the urine output was observed after few days. A further treatment with vasopressin was not undertaken as the osmolality at all times was in normal range.

3-Iodobenzylguanidine↗

Adrenalectomy-induced alterations in glucagon binding and lipolysis in isolated rat adipocytes.

Adipocytes from adrenalectomized rats nearly lost their lipolytic response to glucagon concomitant with a 90% decrease in the number of glucagon receptors per cell. Quantitative analysis of the relation between amount of cell-bound glucagon and hormone-stimulated lipolysis revealed that the ability of the remaining 10% of glucagon receptors to induce lipolysis was not impaired. Binding of the beta-adrenergic antagonist [3H]dihydroalprenolol and maximal lipolysis induced by (-)-isoproterenol, (Bu)2cAMP, 3-isobutyl-1-methylxanthine, and adenosine deaminase were reduced only 10 to 20% after adrenalectomy. Furthermore, glucagon-stimulated cAMP production was greatly decreased in adrenalectomized animals, but isoproterenol-stimulated cAMP production was not. Hydrocortisone replacement in adrenalectomized rats only partially prevented the loss of glucagon receptors and glucagon effects on both cAMP production and lipolysis. These findings suggest that lipolytic cascade distal to hormone receptors was not greatly impaired in adipocytes after adrenalectomy and that the unresponsiveness of these cells to glucagon was mostly due to a marked reduction in the number of glucagon receptors.

1-Methyl-3-isobutylxanthine↗

Adrenalectomy and steroid treatment in obese (ob/ob) and diabetic (db/db) mice.

Adrenalectomy in young obese (ob/ob) and the diabetic (db/db) mouse slowed body weight gain. Treatment of adrenalectomized ob/ob mice with cortisone or deoxycorticosterone acetate (DOCA) significantly increased weight gain in a dose-related manner. Cortisone had no effect on weight gain on lean mice and treatment with dehydroepiandrosterone sulfate was without effect on either ob/ob or lean mice. The increment in body weight of adrenalectomized ob/ob mice treated with corticosterone and DOCA was associated with an increase in body weight and an increase in food intake. When adrenalectomy was performed at twenty-three days of age (five days before weaning), animals carrying the (db/db) genotype remained lighter than their normal littermates. These data document the importance of the adrenal gland and its steroids for the development and maintenance of many features of the obese or diabetes mouse.

Adrenal Glands↗