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Adrenalectomy ameliorates ablative nephropathy in the rat independently of corticosterone maintenance level.

The roles of the adrenal gland and of dietary protein level in ablative nephropathy in the rat were examined by comparing adrenalectomized rats, replaced with corticosterone at low physiological (1 and 2) or high physiological (3 and 4) levels with intact rats (5 and 6). All groups were subjected to 5/6 nephrectomy and followed 12 weeks on a regular diet (2, 4 and 6) or a reduced protein diet (1, 3 and 5). Groups 1, 2, 5 and 6 all grew at the same rate but groups 3 and 4 grew less, though food intake was nearly the same in all. Higher dietary protein, higher corticosterone maintenance level, and the presence of intact adrenal glands all increased proteinuria significantly. Extracellular fluid volume (82Br space) was identical in all groups at 8 and 12 weeks, because the animals were given a choice of water or saline to drink. Mortality was highest (50%) in Group 6 and lowest (11%) in Group 1, but these differences were not significant. Final inulin clearance was significantly improved by adrenalectomy when non-survivors were scored as having zero clearance, but not if the analysis was limited to survivors. It was not affected by diet or by corticosterone level. Renal histopathological scores were also improved significantly by adrenalectomy and by protein restriction, but were not influenced by corticosterone level. Thus adrenalectomy and dietary protein restriction independently ameliorate ablative nephropathy, but corticosterone replacement level has no effects, except on proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Laparoscopic adrenalectomy for phaeochromocytoma: endocrinological and surgical aspects of a new therapeutic approach.

OBJECTIVES: To evaluate the results of laparoscopic resection of phaeochromocytoma with a focus on pre- and intra-operative endocrinological and pharmacological aspects. DESIGN: Retrospective study based on review of case notes and intraoperative anaesthetic records. PATIENTS: Eight patients (four men, four women) aged 13 to 70 (median: 45) years with symptomatic phaeochromocytoma (two patients with MEN IIa syndrome) diagnosed 6-36 months before adrenalectomy in four patients and just before operation in the four remaining patients. All patients presented with hypertension. MEASUREMENTS: Pre- and postoperative blood pressure (BP) was assessed using a sphygmomanometer, intraoperative measurements being obtained by intra-arterial line. Adrenaline (A), noradrenaline (NA), metadrenaline (metA), normetadrenaline (normetA) and vanillylmandelic acid (VMA) were measured in 24-h urine samples. Adrenal imagery consisted in all patients of abdominal computed tomography and [131I] metaiodobenzylguanidine (MIBG) scintigraphy, and in 2 patients, adrenal magnetic resonance imaging and octreotide scintigraphy. Determination of plasma volume was performed by isotopic method. RESULTS: Median (range) preoperative systolic and diastolic BP was 140 (130-240) and 90 (80-150) mm Hg, respectively. Predominant catecholamine secretion consisted of A in four patients (A pattern) and of NA (NA pattern) in the other four. Tumours smaller than 30 mm usually secreted A while larger ones secreted NA. Pre- and intra-operative BP control was straightforward in all but two patients with preferential NA secretion. The median number of systolic and diastolic BP peaks were higher in patients with NA pattern (n = 6, range: 3-9) than in those with A pattern (n = 1.5, range: 1-6). Total duration of pneumoperitoneum ranged from 120 to 240 (median: 195) min. Intra- and post-operative complications included intra-abdominal bleeding, laparoscopically controlled (in one case), and upper pole kidney ischaemia in another. Postoperative hospital stay ranged from 4 to 11 days. All patients were asymptomatic postoperatively and pharmacologically controlled hypertension persisted in two of them. CONCLUSIONS: Laparoscopic adrenalectomy is a safe and efficient technique to remove phaeochromocytoma in terms of intra- and postoperative morbidity, with a low complication rate. Pre- and intra-operative pharmacological blood pressure control is as effective as in conventional adrenalectomy, with greater instability in noradrenaline secreting tumours.

Adolescent↗

Adrenal metastasis from renal cell carcinoma: significance of adrenalectomy.

BACKGROUND: The present study examined adrenal metastasis resulting from renal cell carcinoma (RCC), with the aim of assessing the need for routine ipsilateral adrenalectomy during radical nephrectomy. METHODS: Ipsilateral and contralateral adrenal metastases were investigated in 256 patients with RCC who had undergone radical nephrectomy from 1977 to 1996 at the Tohoku University School of Medicine. RESULTS: Twelve of the 256 patients (4.7%) had adrenal metastasis. Ten of these 12 patients had progressed to disseminated disease with very poor prognosis. Two patients who had solitary adrenal metastases remained disease-free for 21 and 7 years. Four patients showed metastases to the contralateral adrenal gland. Adrenal metastases in seven of 12 patients were identified by pre- or postoperative computed tomography (CT), and in another five macroscopically during surgery. CONCLUSIONS: Adrenalectomy was regarded as a possible curative treatment for patients with solitary adrenal metastasis. However, the incidence of this kind of metastasis was minimal and contralateral adrenal metastases may occur in RCC cases. We therefore believe that adrenalectomy should only be performed if radiographic evidence reveals metastases in the adrenal gland or if gross disease is present at the time of nephrectomy.

Adrenal Gland Neoplasms↗

Adrenalectomy--still a must in radical renal surgery?

OBJECTIVE: To investigate the incidence of adrenal involvement and survival in patients with renal cell carcinoma. PATIENTS AND METHODS: A retrospective, multicentre trial was initiated by the Austrian Association of Urologic Oncology (AUO); between January 1980 and December 1984, 225 patients were eligible for the study. All patients had unilateral renal tumours and nephrectomies were performed either with (group A, 109 patients) or without (group B, 116 patients) adrenalectomy. The two groups were matched for sex, age, laterality and nodal status. The mean follow-up time was 78 months. RESULTS: The location of the intrarenal tumour had no significant effect on adrenal involvement. By univariate and multivariate analysis (Cox's proportional hazards model) significant differences in outcome were found only for pT stages. The mean survival times of patients in group A were 122.9 months in those with stage pT1/2, 76.6 months with stage pT3 and 75.3 months with stage pT4. In group B, survival times were 109 months in those with stage pT1/2 (not significant) and 111 months in stage pT3 (P = 0.0076). Eight patients had adrenal involvement and died from their tumours after a median of 15.3 months (range 4-63). The slightly longer survival of patients in group B with stage T1/2 tumours and the significantly better survival of patients with stage T3 disease may be attributable to statistical bias, but there was no benefit from adrenalectomy. CONCLUSION: The effect of adrenalectomy on the prognosis was at best comparable to that of lymphadenectomy and no curative effect was demonstrated. The removal of a healthy adrenal may be detrimental and cause subsequent problems in those patients requiring hormone replacement.

Adrenalectomy↗

Laparoscopic adrenalectomy: comparison of transperitoneal and retroperitoneal approaches.

OBJECTIVE: To compare the effectiveness and efficiency of transperitoneal anterior laparoscopic adrenalectomy with that of retroperitoneal posterior laparoscopic adrenalectomy. PATIENTS AND METHODS: A retrospective comparison was undertaken of 28 patients who underwent transperitoneal anterior laparoscopy with 22 patients who underwent retroperitoneal posterior laparoscopy between April 1994 and November 2000. There were 18 men and 32 women (mean age 51.0 years, range 23-68) with varying diagnoses. Of the 50 patients, 31 had primary aldosteronism, eight had Cushing's syndrome, three had phaeochromocytoma, one had an 18-hydroxydeoxycorticosterone-induced adenoma and seven had non-functioning adrenal adenoma. Adrenal tumours were confirmed by hormonal assays, biochemical tests and computed tomography. To determine the site of the functioning adenoma, hormones were assayed from adrenal vein sampling. Thirty adrenal tumours were located on the right and 20 on the left. RESULTS: There were no significant differences in general demographic variables between the transperitoneal and retroperitoneal groups. The mean duration of surgery for transperitoneal and retroperitoneal laparoscopy was 202 and 221 min, respectively, and the mean blood loss 113 and 192 mL, respectively. The time to first oral intake, days to full diet, time until ambulatory and duration of hospitalization did not differ significantly between the two approaches. As the body mass index increased, the duration of surgery increased for both approaches. As more procedures were performed the duration of surgery decreased for both approaches. CONCLUSIONS: There were no significant differences between the transperitoneal and retroperitoneal approaches for laparoscopic adrenalectomy.

Adrenal Gland Diseases↗

Adrenalectomy-induced increase of brain protein synthesis is antagonized by corticosterone replacements in free-moving rats.

The autoradiographic method with L-[35S]-methionine was used to determine whether changes in glucocorticoid circulating levels were associated with changes in local rates of protein synthesis in rat brain. Chronic bilateral adrenalectomy induced an increase of methionine incorporation rates into proteins in 60 of the 62 brain regions examined (mean effect, +50%). This effect was confirmed biochemically and quantified by correcting for the relative contribution of methionine derived from protein degradation to the precursor pool for protein synthesis in the whole brain. Acute or chronic administration of corticosterone, at doses that normalize basal levels of adrenocorticotrophic hormone, reversed or prevented the adrenalectomy-induced increase of protein synthesis in most regions. However, in nearly all the regions studied (59 of 62), acute corticosterone administration to sham-operated rats did not change the apparent rate of protein synthesis. These results demonstrate that glucocorticoids exert a generalized inhibitory action on brain protein synthesis, because the stimulatory and persistent effect of adrenalectomy on protein synthesis was antagonized by corticosterone replacements at physiological doses. Thus, the regulation of overall brain protein synthesis by glucocorticoids emphasizes the role of neuroendocrine events on long-term neurochemical processes.

Adrenalectomy↗

Bilateral laparoscopic adrenalectomy: a new treatment for difficult cases of congenital adrenal hyperplasia.

PURPOSE: In difficult cases of congenital adrenal hyperplasia (CAH), often the child may have normal cortisol levels and elevated androgen levels, or normal androgen levels and elevated cortisol levels, but not normal levels of both. Because bilateral adrenalectomy removes the source of the abnormal androgen production, the authors felt that in some cases it might be more efficacious than conventional medical therapy. METHODS: Three children with CAH and suboptimal response to medical management underwent bilateral laparoscopic adrenalectomy. Parents were counseled extensively regarding the experimental nature of this treatment and the potential long-term complications. RESULTS: All children recovered quickly after a mean hospital stay of 1.8 days. Pathologic examination of the removed adrenal glands showed persistent cortical hyperplasia. Follow-up at 6 months indicated marked reduction in abnormal androgen production, which allowed lowering of the steroid dosing to physiologic levels. CONCLUSION: In children with CAH refractory to medical management, bilateral laparoscopic adrenalectomy can be performed safely with almost trivial morbidity. Although early results are very encouraging, the anticipated long-term beneficial effects on growth, short stature, and adult infertility will require years to assess.

Adrenal Hyperplasia, Congenital↗

Studies on hypothalamo-pituitary corticoliberin system. IV. Quantitative changes in ACTH-immunoreactive anterior pituitary cells evoked by long-term intraventricular CRF administration and adrenalectomy.

The aim of the study was to investigate, by coupled immunocytochemical and stereologic methods, the effects of long-term intraventricular administration of ovine CRF (oCRF) on ACTH-immunoreactive cells of the rat anterior pituitary and to compare this effect with that of adrenalectomy. CRF-treated rats received 100 ng of oCRF daily for 8 days while control rats were administered with bovine serum albumin (BSA). After BSA administration number of ACTH-immunoreactive cells/mm2 was greater than in intact rats and CRF lowered their number, however, they were still more numerous than in intact rats. Neither average area nor average volume of studied cells were changed in control and CRF-treated animals if compared with intact ones. The total number of ACTH-immunoreactive cells was higher in the glands of BSA and CRF-treated rats than in intact animals. On the other hand, 60 h after bilateral adrenalectomy a marked increase in both, average area and average volume of ACTH-immunoreactive cells was found. The different response of rat corticotropes to intraventricular CRF administration and adrenalectomy may depend on the presence of operating negative corticosterone feedback in animals with adrenal glands intact. Moreover, the present study revealed the lack of correlation between the average area and average volume of ACTH-immunoreactive cells and the weight of the adrenal gland.

Adrenal Glands↗

Effects of adrenalectomy on urea synthesis in rats.

The effect of depletion of glucocorticoids on the dynamics of hepatic amino-N conversion was examined 2 and 7 days after adrenalectomy in a total of 22 rats substituted by adrenaline. The capacity of urea synthesis was studied by infusion of alanine under steady state conditions with arterial concentrations of alanine between 7.3 and 11.6 mmol/l. The animals were nephrectomized and the capacity was calculated as accumulation of urea in total body water corrected for intestinal hydrolysis. Adrenalectomy reduced the capacity of urea synthesis to 55% of the capacity for control rats and reduced the alanine metabolic rate to 60%. In control rats the urea synthesis exceeded the alanine infusion by indicating an extrahepatic tissue release of amino acids. This difference disappeared after adrenalectomy. The body weight and food intake did not change during the study period. Thus lack of glucocorticoids influences the in vivo nitrogen economy both by decreasing the liver function as to conversion of amino-nitrogen and by decreasing release of tissue amino-nitrogen.

Adrenalectomy↗

Effect of adrenalectomy on the pancreas of db/db mice.

Adrenalectomy has been performed in the diabetic mouse and the islet immunohistochemistry studied. Adrenalectomy restored blood glucose to normal. Mean islet size of diabetic animals was larger than that of either adrenalectomized diabetic animals or of lean controls. Adrenalectomy restored the immunohistochemical appearance of the islets to normal when examined with anti-insulin, anti-glucagon and anti-somatostatin antisera.

Adrenalectomy↗

Essential hypertension: first reason for persistent hypertension after unilateral adrenalectomy for primary aldosteronism?

BACKGROUND: Despite cure of primary aldosteronism by surgical resection, hypertension persists postoperatively in 30% to 50% of patients. The aim of this study was to determine factors influencing long-term outcome of blood pressure after unilateral adrenalectomy for primary aldosteronism. METHODS: Records of 100 patients who underwent unilateral adrenalectomy for primary aldosteronism from 1970 through 1997 were reviewed. Patients were distributed in 2 groups according to whether blood pressure was normal (criteria of World Health Organization). Clinical, biochemical, and pathologic data were compared. RESULTS: All patients were biochemically cured. Blood pressure was normal in 56 patients and improved in 44 (mean follow-up, 69 and 59 months). Persistent hypertension correlated with age, known duration and seriousness of preoperative hypertension, family history of hypertension, no preoperative response to spironolactone, and contralateral adrenal hypertrophy. Gender, surgical approach, and pathologic findings were not predictive factors of blood pressure outcome. The prevalence of hypertension was almost the same in these postoperative patients as the prevalence of essential hypertension in a random population of the same age. CONCLUSIONS: Early unilateral adrenalectomy allows cure or improvement of hypertension in all patients with primary aldosteronism induced by unilateral excessive source of aldosterone secretion regardless of the pathologic findings. Persistent hypertension suggests that coexisting essential hypertension is present.

Adolescent↗

High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: a renewed role for adrenalectomy.

BACKGROUND: Stage IV hormone-sensitive breast cancer is often treated with aromatase inhibitors (anastrozole, letrozole, exemestane), which block the conversion of dehydroepiandrosterone (DHEA) to estrone and estradiol. This is intended to obviate the need for steroid replacement and antiquate adrenalectomy. METHODS: Patients who underwent oophorectomy and were being treated with new aromatase inhibitor therapy received serial measurements of serum estrone, estradiol, and DHEA-sulfate (DHEA-S). Steroid values during responsive and progressive phases of disease were compared. In vitro, human breast cancer cell lines T-47D (estrogen-receptor and progesterone-receptor positive) and HCC 1937 (estrogen-receptor and progesterone-receptor negative) were treated with DHEA-S. Proliferation rates were measured by colorimetric assay. RESULTS: Disease in 12 of the 19 patients progressed. DHEA-S was less than 89 microg/dL in patients during the responsive phase and more than or equal to 89 microg/dL during disease progression, with 1 exception (P < .0005). Estrone and estradiol remained suppressed. After disease progression, the condition of 9 patients stabilized with aminoglutethimide therapy (n = 8) or adrenalectomy (n = 1), and their DHEA-S levels were reduced to less than 89 microg/dL. In vitro, elevated DHEA-S induced cell proliferation in T-47D cells. CONCLUSIONS: DHEA-S levels more than or equal to 89 microg/dL predicted disease progression in states of low estrogen. Tissue culture results supported the role of DHEA-S as an estrogenic agent. Oophorectomies with either aminoglutethimide therapy or adrenalectomy were effective remedies for breast cancer progression due to high DHEA-S.

Adrenalectomy↗

Adrenalectomy and the suppression of memory by puromycin.

It has previously been shown that expression of memory of maze-learning in mice is blocked by puromycin injected intracerebrally one or more days after the training experience. Bilateral adrenalectomy before training has now been found to protect memory against the effects of puromycin. This protection is absent when adrenalectomy follows training. In view of control experiments, we conclude that adrenalectomy before training modifies factors necessary for the expression of memory and that this alteration makes puromycin ineffective in blocking memory.

Adrenal Glands↗

Adrenalectomy decreases nerve growth factor in young adult rat hippocampus.

The effect of adrenalectomy on the level of nerve growth factor (NGF) in the hippocampus and on the distribution of choline acetyltransferase immunoreactivity in forebrain cholinergic neurons of developing rats was studied. Biological and immunohistochemical determinations indicated that in 40-day-old rats, adrenalectomy reduced the NGF level in the hippocampus and the choline acetyltransferase immunoreactivity in the septal lateral bands. Furthermore, autoradiographic studies showed that adrenalectomy causes changes in the distribution and expression of NGF receptors in the hippocampus. These results suggest that adrenal hormones are involved in the regulation of the NGF level in the hippocampus and of NGF receptors in the septum.

Adrenalectomy↗

Maternal bilateral adrenalectomy alters nuclear composition in cerebral cortex of fetal rat.

The present study examined the effects of maternal bilateral adrenalectomy on cell nucleus composition of developing fetal rat cerebral cortex. Pregnant adult rats underwent adrenalectomy (ADX) on day 4 of gestation. Fetal brain tissues from sham and ADX groups were examined at each of 10 embryonal stages, E11-E20. From each fetus three slides of dorsal-central region of developing brain were taken and the diameter and long axis of nucleus of cells in these samples were measured. Maternal adrenalectomy generally produces increased nuclear diameter and number of ovoid nucleus in fetal cerebral cortex especially late prenatal stages. It is shown that ADX may change nuclear composition of developing cerebral cortex.

Adrenal Glands↗

Real indications for adrenalectomy in renal cell carcinoma.

OBJECTIVES: We determined the incidence and characteristics of adrenal involvement in localized and advanced renal cell carcinoma, and evaluated the role of adrenalectomy as part of radical nephrectomy. PATIENTS AND METHODS: From 1993 to 1999, 210 patients with renal cell carcinoma (RCC) (139 men and 71 women, mean age 60.8 years, range 12-96 years) underwent radical nephrectomy with associated adrenalectomy. Patients were divided into two subgroups of 106 with localized (stage T1-2 tumor, group 1) and 104 with advanced (stage T3-4N01M01, group 2) renal cell carcinoma. A retrospective review of preoperative computerized tomography (CT) of the abdomen was performed. Radiographic findings were subsequently compared with postoperative histopathological results to assess the predictive value of tumor characteristics and imaging in determining adrenal metastasis. RESULTS: Of the 210 patients, 15 (7.1%) had adrenal involvement. Tumor stage correlated with probability of adrenal spread, with T3-4 and T1-2 accounting for 13.4% and 0.9% of cases, respectively (p < 0.001). Upper pole intrarenal RCC most likely to spread was local extension to the adrenal gland, representing 53.3% of adrenal involvement. In contrast, multifocal, lower pole and mid region RCC tumors metastasized hematogenously, representing 21.4%, 7%, and 14% of adrenal metastasis, respectively. The relationship between intrarenal tumor size (mean 7.8 cm, range 4-21) and adrenal involvement was not statistically significant. Preoperative CT demonstrated 97.7% specificity, 98.4% negative predictive value, 87% sensitivity and 80% positive value for adrenal involvement by RCC. CONCLUSIONS: Ipsilateral adrenalectomy should only be performed if a lesion is seen preoperatively on CT scan or if gross disease is seen at the time of nephrectomy. The prognosis is poor for RCC with ipsilateral involvement even with complete removal. Because of this poor prognosis we believe that adrenal involvement should constitute a separate stage category.

Adolescent↗

Effects of adrenalectomy on body weight and the size and number of fat cells in the Zucker (fatty) rat.

Adrenalectomy reduced food intake and the rate of weight gain in the Zucker (fatty) rat to levels indistinguishable from normal. The size of adipocytes in the retroperitoneal and perimetrial fat pads also decreased after adrenalectomy but the number of fat cells in each of these depots increased to reach levels not different from those in the sham-operated fatty rat. Fat accretion in the intact fatty rat was characterized by both hyperplasia and hypertrophy of the fat cells, but in the adrenalectomized Zucker rats, weight gain was accompanied by hyperplasia and decreased fat cell size. These data show that adrenalectomy can prevent most of the phenotypic expression of the genetic defect in the fatty rat and challenge the concept that reduced food intake can prevent hyperplasia of fat cells.

Adipose Tissue↗

ACTH immunoactivity in normal rat tissues: modulation by hypophysectomy and adrenalectomy.

This study investigates the effect of pertubation of the normal pituitary-adrenal axis on concentrations of adrenocorticotropin (ACTH)-like immunoactivity in peripheral tissues. We used a polyclonal antibody (West antibody) to measure ACTH-like immunoactivity in glacial acetic acid extracts of five tissues in adult male rats at increasing times (1, 7, 14, and 28 days) after hypophysectomy or adrenalectomy, and in normal control rats. Concentrations of ACTH-like immunoactivity were similar to those previously reported in liver, colon, heart, and small intestine and were not significantly affected by either hypophysectomy or adrenalectomy. While hypophysectomy also had no effect in the kidney, adrenalectomy resulted in a four-fold increase in extractable immunoactivity, first noticeable at seven days (p less than 0.005), but increasing progressively to 28 days (p less than 0.0005). Gel filtration showed that most of the increase in activity in kidneys of adrenalectomized rats corresponded to the 4.5 kD form comprising most of the serum ACTH immunoactivity and suggesting that the activity increase in kidney was largely due to ACTH derived from blood.

Adrenalectomy↗