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Endoscopic retroperitoneal adrenalectomy.

BACKGROUND: The anterior transabdominal approach for adrenalectomy is associated with a longer postoperative recovery period than a posterior extraperitoneal adrenalectomy. The posterior approach is useful for patients requiring bilateral adrenalectomy or in those undergoing unilateral adrenalectomy for benign adenomas smaller than 5 cm. Recently transabdominal laparoscopic adrenalectomy has been used in patients with adrenal tumors. Endoscopic retroperitoneal adrenalectomy (ERA) is an alternative method that provides excellent exposure and should be associated with less postoperative morbidity. METHODS: Between 1993 and 1994 11 ERAs were performed in eight patients in the Department of Surgery, Istanbul Faculty of Medicine. The patients were placed in the prone semijackknife position on the operating table. After the retroperitoneal space was expanded with a balloon trochar, four 10 mm trochars were placed to perform the procedure. RESULTS: Among the eight female patients 23 to 65 years of age (mean, 42 +/- 12.4 years), three had bilateral adrenal hyperplasia caused by Cushing's disease, three patients had functioning adenoma, one patient had nonfunctioning adenoma (three on right and one on left adrenal), and one patient had right adrenal cyst. The mean operation time was 150 minutes (range, 90 to 300 minutes). No changes in PCO2 values have been found during intraoperative blood gas analyses. No intraoperative or postoperative complications occurred. All patients were discharged on the third postoperative day. CONCLUSIONS: ERA is a new and safe method of adrenalectomy. It is less invasive than the posterior approach. Patients treated by ERA seem to experience less postoperative pain and discomfort and have a shorter postoperative hospitalization and recovery period.

Adenoma↗

A posterior lumbar approach for retroperitoneoscopic adrenalectomy: assessment of surgical efficacy.

OBJECTIVES: To compare the efficacy of retroperitoneoscopic adrenalectomy by a posterior lumbar approach (RPA) with that obtained by a transperitoneal anterior approach (TAA) or retroperitoneal lateral flank approach (RLA). METHODS: Fifty-one patients underwent endoscopic adrenalectomy by three approaches, including laparoscopic adrenalectomy by TAA in 33, retroperitoneoscopic adrenalectomy by RLA in 5, and retroperitoneoscopic adrenalectomy by RPA in 13. RESULTS: The average adrenal tumor size was 27 mm (range 8 to 65). The average number of trocars required for RPA was 3.2 which was significantly less than that for TAA and for RLA (4.2 and 4.1, respectively). The conversion rate to open surgery was 9.1% by TAA, 0% by RLA, and 7.7% by RPA. The average operating time for TAA was 252 minutes, which was significantly shortened to 194 minutes by RLA and 142 minutes by RPA (P < 0.02). The average blood loss was 101 mL for TAA and was negligible by RLA and RPA (22 and 32 mL. respectively). CONCLUSIONS: RPA allowed direct access to the main adrenal vascular supply before the gland was greatly manipulated. Endoscopic adrenalectomy by TAA or even by RLA required extra ports for retraction of liver, spleen, vena cava, or adrenal gland, with higher chance of vein avulsion. RPA was technically feasible and most effective for retroperitoneoscopic adrenalectomy in regard to the simplicity of vascular control. The operating time, perioperative morbidity, and cost were reduced with this approach.

Adrenal Gland Neoplasms↗

Reconsidering the necessity of ipsilateral adrenalectomy during radical nephrectomy for renal cell carcinoma.

OBJECTIVES: Ipsilateral adrenalectomy is traditionally advocated as part of radical nephrectomy performed for renal cell carcinoma. The current study addresses the controversy of whether ipsilateral adrenalectomy should be performed routinely during radical nephrectomy. METHODS: A total of 225 patients were treated surgically for renal cell carcinoma over an 18-year period. Of these patients, 158 underwent nephrectomy and simultaneous ipsilateral adrenalectomy and the other 67 had sparing of the ipsilateral adrenal gland. A retrospective analysis of the medical records and assessment of the clinical and the pathologic data were performed. Rates of survival and progression were evaluated in a subgroup of 109 patients, further subdivided into 54 patients who underwent concomitant adrenalectomy and 55 patients with the ipsilateral adrenal preserved during surgery. RESULTS: Histopathologic abnormalities were detected in seven adrenal specimens (4.4%); however, only 3 patients (1.9%) had involvement of the adrenal by renal cell carcinoma. All cases of adrenal involvement were detected by the preoperative imaging modalities. Ipsilateral adrenalectomy did not improve the outcome in comparison to adrenal preservation. CONCLUSIONS: In view of the rarity of ipsilateral adrenal metastasis, the questionable prognostic merits of concomitant adrenalectomy, and the availability of accurate imaging modalities, we conclude that ipsilateral adrenalectomy is not necessary in the majority of the patients undergoing radical nephrectomy for renal cell carcinoma.

Adenoma↗

Laparoscopic adrenalectomy: current status with a review of Japanese literature.

A decade has elapsed since laparoscopic adrenalectomy was first performed in 1992. Accumulated experiences of laparoscopic adrenalectomy have shown superior results to treat small functional benign tumors and make the indication expand to large tumors, pheochromocytomas and localized malignant tumors. Following the initially established transperitoneal approach, which includes anterior and lateral approaches, the retroperitoneal lateral flank and posterior lumber approaches have been performed. Each approach has advantages and disadvantages. The transperitoneal approach supplies a large operative field, many anatomical landmarks and easy handling. But it causes post-operative irritability and it is very difficult to perform after previous upper abdominal surgery. The retroperitoneal approach can be performed even after previous abdominal surgery and patients may be more comfortable after the operation. However, the narrow working space and the lack of anatomical landmarks may increase the rate of intra-operative complications and the rate of conversion to open surgery. Although there is no clear preference between transperitoneal and retroperitoneal approaches, the transperitoneal approach is commonly employed and the transperitoneal anterior approach seems to be the easiest one for right adrenal tumors and the transperitoneal lateral approach for left adrenal tumors. The shorter convalescence with laparoscopic adrenalectomy as compared with open adrenalectomy has been accepted and lower morbidity from laparoscopic adrenalectomy has been achieved. The operative time has been shortened to the level of open adrenalectomy. Less blood loss, less pain and better cosmesis are absolute advantages for the patients. Laparoscopic adrenalectomy is now the gold standard for the treatment of adrenal tumors.

Adrenalectomy↗

Transperitoneal laparoscopic adrenalectomy: experience in 72 procedures.

PURPOSE: To evaluate the safety and effectiveness of transperitoneal laparoscopic adrenalectomy for a variety of adrenal diseases. PATIENTS AND METHODS: Seventy-two patients underwent laparoscopic adrenalectomy from January 1995 until March 1999. The indications for the treatment were limited to either functioning or nonfunctioning adrenal masses without radiologic evidence of involvement of the surrounding tissues. The indication for bilateral adrenalectomy was Cushing's disease after the failure of other therapies or Cushing's syndrome secondary to ectopic ACTH secretion without the discovery of a primary neoplasm. RESULTS: Thirty-five of the adrenalectomies were performed on the left side and 33 on the right side, and 4 were performed bilaterally. The right-sided procedures required a mean operating time of 130 minutes (range 85-200 minutes), the left-sided procedures required a mean operating time of 140 minutes (range 95-200 minutes), and the bilateral procedures required a mean operating time of 240 minutes (range 210-290 minutes). A conversion from laparoscopy to laparotomy was necessary for 3 patients (4%). Intraoperative complications were reported in 6 patients (8%). Postoperative complications likewise occurred in six patients. CONCLUSIONS: These procedures proved to be safe and able to remove the majority of either functioning or nonfunctioning benign adrenal masses. Some controversy remains regarding the safety of laparoscopic adrenalectomy for large lesions and the safety of bilateral laparoscopic adrenalectomy because of bleeding risks, anesthetic risks, and long operative times. The effectiveness of laparoscopic adrenalectomy for nonfunctioning adrenal masses with histologic findings of carcinoma has not yet been proved.

Adolescent↗

Cost-effectiveness of laparoscopic vs open adrenalectomy: small savings in an expensive process.

BACKGROUND AND PURPOSE: Nowadays, laparoscopy has become the approach of choice for adrenalectomy, especially in cases of benign tumors <6 cm. The authors have studied, in a retrospective trial, two groups of patients who have undergone an adrenalectomy: 10 consecutive patients operated on by an open approach and 10 consecutive patients operated on by laparoscopy. METHODS: Laparoscopic adrenalectomies were performed via a transabdominal lateral approach, whereas open adrenalectomies were performed via an anterior transabdominal or posterior retroperitoneal approach. Clinical outcomes were recorded, and special attention was paid to the costs of both techniques, collecting economic data from the costs in outpatient visits, blood and urine tests, diagnostic imaging, hospital admissions prior to surgery, hospital admission for surgery, and surgical expenses. RESULTS: Operative time (110 vs 123 minutes), length of postoperative stay (3.7 vs 5.8 days), and time to oral intake (1 vs 2 days) were significantly lower in the laparoscopic group. From the economic point of view, however, there were no significant differences between laparoscopic and open groups (6,306 vs 7,581), and only surgical inhospital stay costs were significantly lower in the laparoscopic series (742 vs 1,191). All the costs generated by surgery (hospital admission for surgery plus surgical expenses) were smaller in the laparoscopic group but constituted only a small part of the general expenses for these patients. The more expensive part of the budget for every patient was the hospital admissions prior to surgery for diagnosis or preoperative treatment. CONCLUSION: Laparoscopy is a safe and comfortable approach for adrenalectomy and should be the technique of choice. From the economic point of view, laparoscopic adrenalectomy is cheaper than open adrenalectomy, but in all cases, surgical costs are only a minimal part of the budget, and the greater savings must come from the reduction in the presurgical diagnostic process.

Adrenalectomy↗

Outcomes for laparoscopic bilateral adrenalectomy.

BACKGROUND AND PURPOSE: Laparoscopic adrenalectomy has become the preferred surgical approach to manage adrenal disorders. Bilateral adrenalectomy is performed for diseases that are unresponsive to medical management and, frequently, for neoplastic disease. The aim of this study was to review our experience with laparoscopic bilateral adrenalectomy and to evaluate its safety, efficacy, and outcomes. PATIENTS AND METHODS: Between July 1996 and May 2001, five male and two female patients with a mean age of 46 years (range 15-69 years) presented for bilateral adrenalectomy (pheochromocytoma [N = 3], Cushing's disease [N = 3], and metastatic cancer [N = 1]). All procedures were performed using a lateral transperitoneal approach. One gland was excised, the patient was repositioned to the opposite lateral decubitus position, and the remaining gland was removed. RESULTS: Laparoscopic bilateral adrenalectomy was completed in all seven patients. The mean tumor/gland size on the right was 5.0 cm (range 3.1-7.0 cm) and on the left was 5.6 cm (range 3.6-7.0 cm). The mean operative time was 308 minutes (range 190-430 minutes), and the mean estimated blood loss was 138 mL (range 30-300 mL). One patient with a pheochromocytoma experienced intraoperative hypertension necessitating treatment. There were no postoperative complications. The mean postoperative hospital stay was 5.1 days (range 3-9 days). All patients have been treated postoperatively with daily hydrocortisone and fludrocortisone replacement. After a mean follow-up of 33 months (range 2-45 months), six patients are alive. The patient undergoing bilateral adrenalectomy for metastatic lung cancer died from recurrent disease 13 months after resection. CONCLUSION: Laparoscopic bilateral adrenalectomy is safe and effective. Patients are discharged postoperatively in a relatively short time with few complications. Appropriate steroid replacement and close follow-up allows these patients to return to self-reliance.

Adolescent↗

Comparison of clinical outcomes of laparoscopic and conventional open adrenalectomy.

From September 1992 to November 1996, 28 patients underwent laparoscopic adrenalectomy at Osaka University Medical Hospital. They were compared with 25 instances of conventional open surgery performed between May 1990 and April 1996 at the same institution. Laparoscopic adrenalectomy was performed via either a transperitoneal or a retroperitoneal approach. The mean operative time of 375 minutes for laparoscopic adrenalectomy was significantly longer than that of 133 minutes for open surgery. The average hospital stay for laparoscopic surgery was significantly shorter than that of conventional open adrenalectomy. The convalescent period was also significantly shorter in the patients who had laparoscopic adrenalectomy. There was no statistical difference in blood loss during the operation or the number of doses of analgesics administered after operation in the two groups. We conclude that laparoscopic adrenalectomy is one of the options to be selected in surgically managing adrenal tumors. Laparoscopic adrenalectomy could become a standard operative procedure as instruments and techniques of laparoscopy improve significantly.

Adolescent↗

Adrenalectomy for familial pheochromocytoma in the laparoscopic era.

OBJECTIVE: To report the results of treatment of patients with familial pheochromocytomas in the laparoscopic era. SUMMARY BACKGROUND DATA: The optimal surgical management of pheochromocytomas that arise in familial neoplasia syndromes may be complicated by bilateral involvement and associated endocrinopathies. METHODS: Twenty-one patients with familial pheochromocytomas (15 with multiple endocrine neoplasia [MEN] 2A, 4 with MEN 2B, 1 each with von Hippel-Lindau and neurofibromatosis type 1) underwent adrenalectomy between December 1993 and July 2001. Clinical, biochemical, and pathologic data were obtained by retrospective review of perioperative medical records, postoperative biochemical testing, and patient questionnaire. RESULTS: Mean age at diagnosis was 37 +/- 11 years. Twenty of the 21 patients had elevated urine catecholamines, and all had radiographic evidence of an adrenal tumor or tumors. Pheochromocytoma-related symptoms were present in 11 patients (52%). One patient with MEN 2B underwent open adrenalectomy due to previous adrenal surgery and megacolon. Laparoscopic adrenalectomy was attempted in the remaining 20 patients (9 right, 11 left, 2 bilateral). Two patients (9.1%) were converted to open adrenalectomy. Intraoperative hypertensive episodes occurred in 15 patients (71%) and were easily controlled medically. Mean operative time was 216 +/- 57 minutes, mean postoperative length of stay was 3.1 +/- 1.3 days, and mean tumor size was 3.1 +/- 1.0 cm. Minor complications occurred in three patients (14.3%) and major complications in two patients (9.5%). During a mean follow-up of 57 months, a contralateral pheochromocytoma developed in four patients with MEN 2 (33%); three of them underwent adrenalectomy. There have been no long-term complications related to hypertension or adrenalectomy. CONCLUSIONS: This study is the largest series of patients with familial pheochromocytoma undergoing adrenalectomy during the laparoscopic era. The results suggest that the laparoscopic approach is safe and effective for managing unilateral or bilateral adrenal medullary disease in this population.

Adrenal Gland Neoplasms↗

Adrenal metastases in 1635 patients with renal cell carcinoma: outcome and indication for adrenalectomy.

PURPOSE: Routine removal of the ipsilateral adrenal gland in patients with renal cell carcinoma who undergo nephrectomy has been a matter of dispute. In a retrospective study we screened for subgroups of patients with renal cell carcinoma from a large single center patient population who may have benefited from ipsilateral adrenalectomy. MATERIALS AND METHODS: Radical nephrectomy was performed in 1635 patients at a single institution between 1980 and 2000. A total of 1010 patients underwent radical nephrectomy plus ipsilateral adrenalectomy, whereas in 625 no simultaneous adrenalectomy was performed. Numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods for their predictive value in regard to cancer specific survival. RESULTS: Metastases in the adrenal gland were found in 5.5% of patients (56 of 1010) undergoing nephrectomy with adrenalectomy. Of 30 patients with adrenal metastasis and preoperative computerized tomography/magnetic resonance imaging 23 were found to have histological evidence of cancer, approaching a false-negative rate of 23.3%. All patients with false-negative computerized tomography/magnetic resonance imaging had a primary tumor of greater than 4 cm. Patients with adrenal metastases predominately had pT3 or greater tumor stage (82%). Cancer specific survival rates (75% vs 73% for adrenalectomy vs no adrenalectomy) and postoperative complications rates (7% vs 8%) did not differ significantly between the 2 groups. The prognosis in patients with a solitary adrenal metastasis (18 of 56) was more favorable than in patients with additional metastatic sites (38 of 56). CONCLUSIONS: Adrenal metastases from primary renal cell carcinoma were found significantly more often in patients with advanced tumor stages. Ipsilateral adrenalectomy should be recommended for all resectable renal cell carcinoma with a primary tumor of greater than 4 cm or with nonorgan confined tumor stages (T3 or greater) since a false-negative rate of about 20% can be expected with current imaging techniques.

Adrenal Gland Neoplasms↗

Laparoscopic adrenalectomy for adrenal carcinoma and metastases.

PURPOSE OF REVIEW: This review article discusses topics concerned with laparoscopic adrenalectomy for adrenal pathologies. RECENT FINDINGS: Over the past decade, laparoscopic adrenalectomy has become the operation of choice for the resection of adrenal tumors, and provides dramatically reduced morbidity associated with the operation. Although current laparoscopic adrenalectomy for metastatic or primary adrenal malignancy is a feasible procedure, great care is required. Laparoscopic adrenalectomy for these adrenal pathologies should be converted to open adrenalectomy or hand-assisted laparoscopic adrenalectomy for difficult dissection, invasion, adhesions or surgeon inexperience. In general, laparoscopic adrenalectomy can be performed with acceptable outcomes in carefully selected patients with small, organ-confined, solitary adrenal metastasis or primary adrenal carcinoma. SUMMARY: As surgical technique and complete resection are crucial to the success of the procedure, appropriate and careful judgment on the part of the surgeon is the most important factor in the care of a patient with such adrenal malignancies.

Adrenal Gland Neoplasms↗

A population of non-luteinising hormone/non-adrenocorticotrophic hormone-positive cells in the male rat anterior pituitary responds mitotically to both gonadectomy and adrenalectomy.

The male rat anterior pituitary responds highly reproducibly to specific hormonal stimuli in terms of the extent and timing of mitotic and apoptotic (trophic) activity. The principal objective of the present study was to define the contribution of hormonally identifiable cells to the trophic responses to bilateral gonadectomy and bilateral adrenalectomy. The patterns of pituitary mitotic responses to adrenalectomy and gonadectomy are similar in amplitude and duration. When adrenalectomy and gonadectomy are combined, the amplitude of the pituitary mitotic response is unchanged. That is, the trophic stimuli are not additive. Dexamethasone-induced apoptosis in nascent cells is amplified not only by recent adrenalectomy, but also, and to an almost identical extent, by gonadectomy. Combining adrenalectomy and gonadectomy does not further enhance the size of the apoptotically-responsive cell population. Dual bromodeoxyuridine and adrenocorticotrophic hormone (ACTH) or luteinising hormone (LH) immunolabelling showed that more than 95% of all dividing cells are not and do not become positive for either of these hormones during the period of peak mitotic response. Following adrenalectomy, most newly-formed ACTH cells are derived from differentiation of pre-existing hormonally undifferentiated cells. Despite an overall increase in mitotic activity, there is no measurable increase in the number of LH immunopositive cells after gonadectomy. The nonadditive pituitary mitotic and apoptotic responses to adrenalectomy and gonadectomy strongly suggest that the same progenitor cell population responds mitotically to both. This weakens the prevailing view that hormonally identifiable cells with specific trophic profiles contribute significantly to pituitary cell subpopulation revision.

Adrenal Glands↗

Effect of adrenalectomy and high-fat diet on the fatty Zucker rat.

Lean and obese Zucker fatty rats were adrenalectomized or sham operated at 10 wk of age. At 15 wk one-half of each group was placed on a high-fat diet. At 32 wk of age the experiment was ended. Several conclusions can be drawn about the effects of adrenalectomy, high-fat diets, and their interaction in the Zucker fatty rat. First, adrenalectomy slowed the weight gain in both obese fatty rats and in the lean animals, although the effect was greater in the fatty rats. Second, weight gain was accelerated in intact lean and fatty rats eating a high-fat diet. Third, adrenalectomy attenuated the weight gain associated with a high-fat diet and reduced the body content of fat and protein in the lean animals and fatty rats fed the low-fat diet. Fifth, adrenalectomy significantly affected the retroperitoneal and subcutaneous fat depots but not the epididymal fat depot. Sixth, adrenalectomy decreased fat cell number in retroperitoneal and subcutaneous fat depots, but this was much less evident in the epididymal fat depot. Seventh, lipoprotein lipase activity expressed per milligram protein increased after adrenalectomy in the fatty rat but was reduced on the same basis in lean animals regardless of diet. Finally, the increase in retroperitoneal lipoprotein lipase activity expressed per fat cell observed in lean animals fed the high-fat diet was not observed in the fatty rat. These studies show that a high-fat diet and adrenalectomy interact in the development of obesity in both lean and fatty Zucker rats.

Adipose Tissue↗

Adrenalectomy of the obese Zucker rat: effects on the feeding response to enterostatin and specific mRNA levels.

The effects of adrenalectomy on the feeding response to enterostatin and the mRNA levels of its parent protein, pancreatic colipase, have been investigated in lean (fa/?) and genetically obese (fa/fa) rats. Adrenalectomy reduced body weight gain and food intake of obese rats. Enterostatin inhibited the intake of high-fat diet in obese rats but not in lean rats. Adrenalectomy reduced food intake of all rats and abolished the response to enterostatin in the obese group. Obese rats had low levels of colipase mRNA, but these were normalized after adrenalectomy. The ability to respond to exogenous enterostatin is possibly linked to low levels of production of the peptide. The effects of adrenalectomy on brown adipose tissue uncoupling protein (UCP) mRNA and beta 3-adrenergic receptor (beta 3-AR) mRNA were also investigated. Northern blot analysis showed low levels of both UCP mRNA and beta 3-AR mRNA in obese rats that were restored to or toward the normal levels of lean rats by adrenalectomy. Adrenalectomy had no significant effects on mRNA levels in lean rats.

Adipose Tissue, Brown↗

Effect of adrenalectomy on membrane properties and synaptic potentials in rat dentate granule cells.

Adrenalectomy is known to accelerate both neurogenesis and cell death of granule cells located in the suprapyramidal blade of the rat dentate gyrus. Three days after adrenalectomy, some granule cells have already died by apoptosis while newly formed cells are not yet incorporated in the cell layer, resulting in a temporary loss of granule cells. Concomitantly, the field response to stimulation of perforant path afferents is reduced. While the temporary cell loss is likely to attenuate synaptic field responses, adrenalectomy-induced changes in properties of the surviving cells may also contribute to the reduction in field response amplitude. To address this possibility, we here investigated the membrane properties and synaptic responses of dentate granule cells, 3 days after adrenalectomy. We found that passive and most of the active membrane properties of granule cells in adrenalectomized rats were not significantly different from the cell properties in sham-operated controls. However, intracellularly recorded synaptic responses from surviving granule cells were markedly reduced after adrenalectomy. The N-methyl-D-aspartate (NMDA)- and the non-NMDA receptor-mediated components were reduced to a similar extent, suggesting that the attenuation of synaptic transmission after adrenalectomy could be partly of presynaptic origin. The data indicate that the earlier observed attenuation of synaptic field responses after adrenalectomy may be partly due to a diminished glutamatergic input to the dentate gyrus and not exclusively to a loss of granule cells participating in the synaptic circuit.

Action Potentials↗

Involvement of vasopressin in the down-regulation of pituitary corticotropin-releasing factor receptors after adrenalectomy.

The role of vasopressin (VP) in the regulation of pituitary corticotropin-releasing factor (CRF) receptors was studied by examining the effects of adrenalectomy and VP infusion on pituitary CRF receptors in genetically VP-deficient rats (di/di) and Long-Evans control rats. Binding studies with [125I]Tyr-ovine CRF in 30,000 X g anterior pituitary membrane-rich fractions revealed similar characteristics for the CRF receptors in Long-Evans and di/di rats, with Kd values of 2.4 +/- 0.6 and 1.9 +/- 0.2 nM, respectively, and receptor concentrations of 278 +/- 31 and 286 +/- 43 fmol/mg, respectively. Two days after adrenalectomy, the pituitary CRF receptor concentration decreased by 72 +/- 4.2% in Long-Evans rats, but by only 20.3 +/- 5.6% in di/di rats. CRF receptor affinity was unchanged after adrenalectomy (Kd = 1.7 +/- 0.5 nM; n = 8). To determine whether VP deficiency is responsible for the smaller decrease in CRF receptor in di/di rats, the effect of exogenous VP infusion (100 ng/min) by sc osmotic minipumps was studied in adrenalectomized di/di rats. Two days after adrenalectomy, pituitary CRF receptors were reduced by 21 +/- 8% in control di/di rats, whereas a 77.7 +/- 1.8% decrease was observed in VP-infused di/di rats, comparable to the effect of adrenalectomy in Long-Evans rats. VP infusion also caused a significant 35 +/- 2% decrease in CRF receptors in the pituitaries of sham-operated di/di rats, with no change in CRF receptor affinity. In Sprague-Dawley rats, VP or CRF infusion (100 ng/min) decreased pituitary CRF receptors by 14 +/- 1.9% and 46 +/- 3%, respectively. However, the combined infusion of both peptides caused a 65% +/- 4.2 decrease, similar to that observed after adrenalectomy. In vitro incubation of quartered pituitaries with VP or CRF for 4 h reduced CRF receptors by 23.1 +/- 8.2% and 38.2 +/- 3.8%, respectively, while simultaneous preincubation with both peptides was followed by a decrease of 55.3 +/- 5.3%. These findings indicate that increased hypothalamic release of VP contributes to the down-regulation of pituitary CRF receptors after adrenalectomy.

Adrenalectomy↗

Patient's age is a simple predictive factor for the development of Nelson's syndrome after total adrenalectomy for Cushing's disease.

Reportedly between 8-38% of patients who receive bilateral adrenalectomy for treatment of Cushing's disease will develop Nelson's syndrome. We investigated which factors may predict the development of the syndrome. Eight of 48 patients, bilaterally adrenalectomized for pituitary-dependent Cushing's syndrome 1-30 yr previously, developed Nelson's syndrome 1.5-13 yr (6.6 +/- 4.3 yr) after adrenalectomy. The mean age at adrenalectomy in the group of patients who developed Nelson's syndrome was significantly lower than that in the group without the syndrome (mean +/- SD, 26.0 +/- 6.0 and 35.6 +/- 11.7 yr, respectively; P < 0.02). In the patients adrenalectomized before the age of 35 yr, 8 of 27 (30%) developed Nelson's syndrome, whereas in the patients older than 35 yr, no one did (P < 0.02). No statistically significant differences between the two groups were found in sex ratio, duration of disease before adrenalectomy, or duration of follow-up thereafter. There were no statistically significant differences between the two groups in mean plasma cortisol and ACTH levels before adrenalectomy, cortisol suppressibility after the administration of 8 and 16 mg dexamethasone, or cortisol responses to CRH, TRH, and LH-releasing hormone before adrenalectomy. We conclude that age at the time of adrenalectomy is an important predictive factor for the development of Nelson's syndrome.

Adolescent↗

Adrenalectomy induces a decrease in the light scatter properties and amylase content of isolated zymogen granules from rat pancreas as analyzed by flow cytometry.

The effect of glucocorticoid deprivation induced in male rats by adrenalectomy on the pancreatic zymogen granules was studied. Zymogen granules were purified from control, sham-operated and adrenalectomized animals studied 1, 3 and 7 days after surgery. The zymogen granules were characterized by flow cytometry, and in each granule the size (based on the forward or low angle light scatter (FSC) parameter), membrane complexity (based on side or 90 degrees light scatter (SSC) parameter) and amylase content were evaluated. Amylase content/DNA ratio in pancreatic homogenates was also analyzed. The zymogen granules of the control rats were found to be distributed in two populations: a major one-R1 (95.45 +/- 1.21%)-containing zymogen granules with a smaller mean size and complexity, and a minor population-R2 (4.45 +/- 0.24%)-the granules of which had a mean size which was larger and more complex. At day +1 after adrenalectomy the zymogen granules were significantly (P < 0.05) smaller than those of control animals. The R2 zymogen granules were similar to those from R1 as regards their size, but were more complex, suggesting that the immediate effect of glucocorticoid deprivation is to induce a depletion of the larger granules presumably belonging to the R2 population. The amount of amylase per granule did not vary at day +1 after adrenalectomy, although the amylase content/size ratio per granule was significantly (P < 0.001) increased. This mechanism could be explained in terms of the existence of a bypass defined in the adrenalectomized animals between the granular content and cytosolic enzymes. Prolongation of the adrenalectomy period to 3 and 7 days resulted in a progressive increase in zymogen granule size and complexity, both parameters showing similar characteristics to those of the controls at day +7 after adrenalectomy. However, the percentage of zymogen granules within the R1 and R2 populations was clearly different from that of controls since the R2 population was much more numerous (11.25 +/- 0.75% and 15.25 +/- 1.15% (adrenalectomized rats at days +3 and +7 respectively) versus 4.45 +/- 0.24% (controls)). An increase in the content of amylase per DNA was observed in adrenalectomized rats at day +1 although this transient effect cannot be related to glucocorticoid deprivation because it was also observed in sham-operated rats (day +1). However, a significant reduction, nearly 64%, in the amylase content/DNA ratio is produced by the absence of glucocorticoids 7 days after adrenalectomy and this is associated with a reduction in the content of amylase in each individual zymogen granule which reaches a minimum 3 days after adrenalectomy. It should be noted that, despite this, the enzyme concentration in each granule remains constant as there is a parallel decrease in the zymogen granule amylase content and size.

Adrenalectomy↗