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The effects of adrenalectomy on the ontogenesis of brain: noradrenaline and dopamine content.

The effect of adrenalectomy on catecholamine content in the diencephalon and the rest of the brain of male and female rats during the post-natal period was studied. Seven days after adrenalectomy, there is no change in noradrenaline or dopamine content. However, the dopamine levels of both the diencephalon and the rest of the brain decrease with age between days 45 and 60, while noradrenaline content in the diencephalon and the rest of the brain remained unchanged. Thus adrenalectomy significantly affected the developmental pattern of brain dopamine.

Adrenalectomy↗

Glucocorticoid receptor regulation: the effects of adrenalectomy, exogenous glucocorticoid, and stress on hepatic receptor number in male and female mice.

Although glucocorticoids are known to regulate their own receptor number, the physiologic significance of this process is not known. In order to assess this process in intact animals the effects of adrenalectomy, stress, and exogenous glucocorticoid on the number of hepatic glucocorticoid receptors in Swiss-Webster mice were evaluated. In males 24 hr after adrenalectomy there was a clear 2- to 2.5-fold increase (upregulation) in glucocorticoid receptor number. Conversely, 24 hr after the ip administration of exogenous corticosterone there was a clear downregulation of receptor number. In each case (upregulation and downregulation) female mice were much less responsive than males. Three stressors were used to evaluate the effect of the endogenous secretion of glucocorticoids on downregulation. Male mice were exposed to ether, vibration, and confinement either once or daily for periods up to 3 days. Animals were sacrificed 24 hr after the last stress and hepatic receptor number was compared to an unstressed control. Cytosolic receptor number was not influenced by any of these stimuli. It is concluded that although glucocorticoids clearly regulate glucocorticoid receptor number, as demonstrated by adrenalectomy and the administration of steroids to adrenalectomized animals, the physiologic significance of this process is uncertain as receptor number does not appear to be changed by stimuli of adrenal glucocorticoids in the intact animal.

Adrenalectomy↗

Intravenous methylene blue as an aid to intraoperative localization and removal of the adrenal glands during laparoscopic adrenalectomy.

BACKGROUND: We hypothesized that intravenous methylene blue will facilitate adrenal gland identification and resection during laparoscopic adrenalectomy. METHODS: Five mini-Hanford pigs were anesthetized and monitored per an approved Internal Review Board protocol. Timing of color changes in the adrenals was recorded after administering methylene blue at three different doses: 2.5 mg/kg, 5.0 mg/kg, and 7.5 mg/kg. The time required for laparoscopic adrenalectomy with and without methylene blue was recorded. RESULTS: No color change occurred after the 2.5 mg/kg dose. For the 7.5 mg/kg versus the 5.0 mg/kg dose there was a more rapid bluish color change (mean time, 1.89 minutes versus 3.45 minutes; P = 0.03) and a longer duration of bluish color change (mean time, 12.20 minutes versus 6.19 minutes; P = 0.01). Laparoscopic adrenalectomy using methylene blue resulted in a 34.5% faster median resection time (10.13 minutes versus 15.47 minutes). CONCLUSIONS: Methylene blue concentrates in the adrenal glands and facilitates identification and resection of the adrenal glands by a laparoscopic approach.

Adrenal Glands↗

Laparoscopic adrenalectomy for malignancy.

The superiority of the minimally invasive approach to adrenal resections has been well documented for benign pathology. With technical advances and increased experience, surgeons have successfully performed laparoscopic adrenalectomies for metastatic and primary malignancies of the adrenal gland. The technique of laparoscopic adrenalectomy as it pertains to malignant lesions is presented. A review of the literature demonstrates the safety and efficacy of laparoscopic adrenalectomy for metastatic colorectal, lung, and renal tumors. For primary adrenal malignancies, radical resections can be effectively performed laparoscopically; however, continued long-term follow-up is needed to establish the minimally invasive technique as the preferred approach.

Adrenal Gland Neoplasms↗

Adrenal lesions assessed in the era of laparoscopic adrenalectomy: a modern day series.

BACKGROUND: To evaluate if laparoscopic adrenalectomy (LA) has changed the indications for adrenalectomy. METHODS: Retrospective analysis of patients with adrenal lesions referred from 1992 to 2004. Patients were divided into 2 groups, those before and those after the introduction of LA. RESULTS: One hundred eighty patients were assessed. Functioning lesions were found in 120 (66%) patients. Sixty patients had nonfunctioning tumors. Before the introduction of LA, 13% had primary hyperaldosteronism (PA), 23% had pheochromocytoma (Pheo), 20% had Cushing's syndrome (CS), and 7% had adrenal cortical cancer (ACC). No difference was seen in the percentage of patients referred after LA with Pheo (20%), CS (16%), or ACC (6%). There was, however, a significant increase in the percentage of patients referred with PA after introducing LA (13% vs. 27%), P < .05. CONCLUSION: Indications for adrenalectomy have not changed since introduction of LA. There was, however, an increased percentage of patients with PA referred since the introduction of LA.

Adrenal Gland Neoplasms↗

Pre- and postsynaptic dopamine mechanisms after repeated nicotine: effects of adrenalectomy.

The reinforcing properties of nicotine may be related to its ability to release dopamine in the nucleus accumbens and to increase locomotor activity in experimental animals. Both these effects are sensitized following repeated drug exposure, a phenomenon that may underlie important aspects of addiction. Adrenal steroids may be involved both in positive reinforcement and in sensitization. Adrenalectomy hampers, e.g., the induction of locomotor sensitization to nicotine, and cross-sensitization between stress and psychostimulants may develop. Here, the effect of adrenalectomy on postsynaptic and presynaptic changes of the mesolimbic dopamine system in association with nicotine sensitization was examined. Adrenalectomy or sham-operated rats received daily nicotine (0.4 mg/kg s.c.) or vehicle for 15 days, after which the locomotor responses to nicotine (0.2 mg/kg s.c.) and the dopamine D1/D2 receptor agonist apomorphine (1.0 mg/kg s.c. or 100 microM in the nucleus accumbens by reversed microdialysis) were recorded. In addition, accumbal dopamine output was monitored by in vivo microdialysis after nicotine challenge. Sham/nicotine animals showed a sensitized locomotor response to systemic and local apomorphine compared to all other groups, including the adrenalectomized/nicotine group. Nicotine increased accumbal dopamine output in all animals. In contrast, nicotine induced a pronounced increase in locomotor activity in the sham/nicotine animals compared to the other vehicle group and the adrenalectomized animals. These results indicate that adrenal steroids are involved in the induction of the postsynaptic component of nicotine sensitization, whereas their involvement in tentative presynaptic changes remains unclear.

Adrenalectomy↗

Adrenalectomy affects pain behavior of rats after formalin injection.

Stressful stimuli can activate the hypothalamo-pituitary-adrenal-axis and the endogenous opioid system. In addition, corticosterone and opioid release might cause analgesia. This rat study used adrenalectomy for corticosterone withdrawal and naloxone administration for opioid antagonism in order to study pain behavior and hypophyseal hormone release in the plasma after a formalin test. Twelve days before the formalin testing, male Sprague Dawley rats underwent adrenalectomy or sham-adrenalectomy, and non-operated rats were used as reference. The number of flinches and the duration of licking or biting behavior were measured during the early and late phase. In reference and sham-operated rats, injection of formalin 5% resulted in a marked pain behavior in the early and late phase with significant increases in ACTH and corticosterone plasma levels. In adrenalectomized rats, pain behavior was decreased during both phases. Naloxone, administered before the late phase, did not alter pain behavior in sham or reference rats, whereas in adrenalectomized rats pain reactivity returned to those levels observed in reference rats. Beta-endorphin plasma levels above the detection limit were more frequently found in adrenalectomized rats. Thyrotropin and prolactin levels were not different between studied groups. We speculate that the observed reduced pain behavior in adrenalectomized rats after formalin, is the result of an increased production of pro-opiomelanocortin, the pro-drug of both adrenocorticotrophic hormone and beta-endorphin.

Adrenalectomy↗

Adrenalectomy for solitary adrenal metastases from non-small cell lung cancer.

BACKGROUND: The treatment of patients with adrenal metastases from lung cancer (non-small cell lung cancer, NSCLC) remains controversial. Several studies of adrenalectomy in cases of isolated adrenal metastases from NSCLC suggest that these patients could have improved survival. Our aim is to define the history of patients after resection of solitary metastases to the adrenal gland and to identify characteristics of patients who achieved prolonged survival. METHODS: Between January 1997 and July 2000, 11 patients underwent curative resection for metastatic NSCLC of the adrenal gland in our institution. In all patients who were accepted for curative adrenalectomy, the primary NSCLC had been treated by complete resection. RESULTS: Eleven patients (seven men and four women) with unilateral adrenal metastases of NSCLC entered the study. Median age was 59 years (range 47-67 years). There was no perioperative death. The overall median survival after metastasectomy was 12.6 months (CI: 9.2-16.1 months). Patients with curative resection and metachronous disease (n=6) had a median survival of 30.9 months and tended to do better than patients with synchronous adrenal metastases (n=5) (median survival: 10.3 months). CONCLUSIONS: We conclude that adrenalectomy for clinically solitary, resectable metastases can be performed safely. It appears reasonable that such selected patients should be considered surgical candidates.

Adrenal Gland Neoplasms↗

Adrenalectomy-induced ZnT3 downregulation in mouse hippocampus is followed by vesicular zinc depletion.

The effects of adrenalectomy (ADX) on the vesicular zinc content of zinc-enriched (ZEN) terminals in mouse hippocampus were investigated at light microscopic levels using zinc transporter-3 immunohistochemistry (ZnT3IHC) and zinc selenium autometallography (ZnSeAMG). ZnT3 resides in the synaptic vesicle membranes of ZEN neurons and is believed to move zinc ions into the vesicles. ZnT3IHC staining closely corresponds to the ZnSeAMG staining, but in the present study we present evidence of a delayed decrease of ZEN zinc, as compared to downregulation of the ZnT3 protein following ADX. Twenty-four hours after adrenalectomy the level of ZnT3IHC was visibly reduced while the ZnSeAMG staining intensity seemed unchanged. After 10 and 30 days, however, downregulation of ZnT3 was paralleled by a distinct reduction in ZnSeAMG staining. The total protein concentration of ZnT3 was reduced by about 53%, and the total zinc concentration in the hippocampus of the same mice was reduced by 43-64%, 30 days after the adrenalectomy. The present results support previous results suggesting that ZnT3 is responsible for transport of zinc ions into a pool of synaptic vesicles in ZEN terminals.

Adrenalectomy↗

Critical size of residual adrenal tissue and recovery from impaired early postoperative adrenocortical function after subtotal bilateral adrenalectomy.

BACKGROUND: Subtotal bilateral adrenalectomy may preserve adrenocortical function. Little is known about the early postoperative function of the adrenal remnant. METHOD: In 10 patients with bilateral adrenal tumors (pheochromocytomas, adrenocortical nodular hyperplasia, and adrenal metastases), plasma adrenocorticotropic hormone (ACTH), serum cortisol, and maximal cortisol liberation were examined with an ACTH test after subtotal bilateral adrenalectomy, which left 15% to 30% of adrenal tissue in situ. RESULTS: In the early postoperative period, all patients had normal basal serum cortisol levels (mean, 415+/-208 nmol/L; normal morning range, 138-690 nmol/L) but pathologically increased plasma ACTH levels (mean, 55+/-42 pmol/mL; normal, <10.1 pmol/L). In 6 patients, a pathologic ACTH test result was observed. During follow-up (mean, 11.3+/-7.6 months), all patients were found to have a normal ACTH test result. None of the patients required steroid supplementation. However, in patients with both familial pheochromocytoma and impaired adrenocortical function during the early postoperative period, the maximal increase of serum cortisol after ACTH stimulation was significantly reduced (mean, 301+/-86.8 nmol/L) compared with control subjects (mean, 490+/-132.6 nmol/L; P=.019). CONCLUSION: After subtotal bilateral adrenalectomy left 15% to 30% of adrenal tissue in situ, functional recovery could be observed in all patients. However, subclinical impairment of the adrenocortical function with questionable clinical significance has to be considered in some of the patients. Especially during the early postoperative period, careful observation of the patients without exogenous steroid administration is required.

Adrenal Cortex Function Tests↗

[Lessons learned from 274 laparoscopic adrenalectomies].

AIMS: To define the role of minimally invasive video-assisted surgery in the surgical management of adrenal disease and discuss the respective indications of the trans and retroperitoneal video assisted approaches. MATERIALS AND METHODS: During the last 8 years (1994-2001), 330 adrenalectomies were performed in 305 patients: 274 (83%) laparoscopic approaches and 56 (17%) open approach. Open surgery was reserved for patients presenting with large or malignant tumours (29 cases), multiple and/or extraadrenal phaeochromocytomas (13 cases), previous intraabdominal intestinal surgery (10 cases), and in those requiring concomitant intraabdominal surgery (4 cases). Laparoscopic adrenalectomy was performed using the lateral transperitoneal approach for 89 Conn's syndrome, 67 Cushing's syndrome, 2 virilizing tumours, 51 phaeochromocytomas and 65 non secretory tumours greater than 4 cm in diameter. Nineteen patients underwent bilateral adrenalectomy. RESULTS: There were no deaths. Twenty patients (7.3%) had a complication. Eleven cases required open conversion (4%) because of difficulties with dissection (8 cases), preoperative suspicion of malignancy (2 cases), and one pneumothorax. The average size of tumours was 34 mm (7-110 mm). There were 18 malignant tumours (6.5%): 8 adrenocortical carcinomas, 1 leiomyosarcoma, and 9 metastases. All patients with hormonally secreting tumours were cured of their endocrinopathy. There was 1 death secondary to hepatic metastases in a patient with an adrenocortical carcinoma. CONCLUSION: Most adrenal tumours are suitable for video assisted excision. The only absolute contraindication is an invasive carcinoma requiring an extended excision. The lateral, transperitoneal approach is the most suitable for tumours greater than 5-6 cm in diameter. Both the transperitoneal or retroperitoneal approaches are suitable for smaller tumours depending on operator choice and experience. However in the presence of a large right lobe of liver or previous intraabdominal surgery the retroperitoneal approach may be preferable.

Adrenal Gland Diseases↗

Adrenalectomy for a solitary adrenal metastasis from lung cancer.

BACKGROUND: Several case reports have shown that patients with truly solitary adrenal gland metastases can undergo resection with long-term survival. METHODS: We assessed consecutive patients with operable or operated non-small cell lung cancer in whom the presence of a unilateral solitary adrenal metastasis was confirmed histologically. Synchronous homolateral adrenal metastases were resected at the same time as the non-small cell lung carcinoma through a transphrenic approach. Synchronous contralateral or metachronous adrenal metastases were resected through an elective approach. RESULTS: Of 598 patients with operable or operated non-small cell lung carcinoma, 11 had a unilateral solitary adrenal gland metastasis and underwent adrenalectomy with no additional mortality or morbidity. One patient died of late postoperative complications and 7 patients died of other distant metastases between 4 and 24 months after adrenalectomy. Two patients are still alive and free of recurrent disease and 1 patient is still alive with brain metastasis 66, 6, and 10 months, respectively, after adrenalectomy. CONCLUSIONS: In the absence of selection criteria to identify the subgroup of patients who will benefit from surgical resection, we suggest the resection of synchronous lesions in patients without N2 involvement and the careful selection of patients with metachronous adrenal metastases according to the evolution of their disease.

Adrenal Gland Neoplasms↗

Rat hypothalamic proopiomelanocortin messenger RNA is unaffected by adrenalectomy.

The negative feedback control of hypothalamic cortocotrophin releasing factor (CRF) and anterior pituitary proopiomelanocortin (POMC) by corticosteroids is well understood. However, less is known about the mechanisms that regulate POMC gene expression in the arcuate nuclei in the medial basal hypothalamus (MBH). Using a sensitive and specific S1 endonuclease protection assay, we have examined the effect of adrenalectomy on POMC mRNA in the rat MBH and pituitary. Our results show that adrenalectomy does not change POMC mRNA levels in the MBH at 7 or 14 days post surgery. The neurointermediate lobe of the pituitary was similarly unaffected by adrenalectomy, while in the anterior lobe, POMC mRNA increased 7-10 fold at both time points, effects that were prevented by dexamethasone treatment. We conclude that while POMC mRNA in the anterior lobe of the pituitary is regulated by plasma glucocorticoids, in the MBH and neurointermediate lobe, it is not.

Adrenal Glands↗

Laparoscopic adrenalectomy: the retroperitoneal approach.

PURPOSE: Retroperitoneal laparoscopy, by providing direct access to the retroperitoneal cavity, is an interesting approach to urological surgery. We report our initial experience with retroperitoneal laparoscopic adrenalectomy. MATERIALS AND METHODS: Between January 1995 and April 1997, 23 adrenalectomies were performed by retroperitoneal laparoscopy in 10 men and 12 women. The patients were placed in the lateral decubitus position and 5 trocars were used. The retroperitoneal working space was created by digital dissection and was completed by insufflation without balloon dissection. The surgical indications were Conn's adenoma in 12 cases, Cushing's adenoma in 4, bilateral adrenal hyperplasia (Cushing's disease) in 1 (treated in a single procedure), a nonfunctioning adenoma in 2, pheochromocytoma in 2 and adrenal metastasis in 1. RESULTS: We removed 7 right and 16 left adrenal glands in an average operating time of 97 minutes (range 45 to 160). Average tumor size was 26 mm. (range 10 to 40). Average hospital stay was 3.3 days (range 1 to 10). Blood loss was minimal. Postoperative analgesic requirements were moderate. Conversion to open surgery was not necessary. The morbidity rate was low, with 1 postoperative hematoma and 1 case of persistent fever (greater than 38.5C). CONCLUSIONS: Retroperitoneal adrenalectomy is a reliable and effective technique. At our institution retroperitoneal laparoscopy is now the standard adrenal surgery procedure for tumors less than 5 cm.

Adenoma↗

Intraoperative ultrasound aids in dissection during laparoscopic partial adrenalectomy.

PURPOSE: Adrenal cortical sparing surgery is a relatively new approach to adrenal tumors. Laparoscopic partial nephrectomy is a technically feasible but challenging operation. We describe the use of intraoperative ultrasound to facilitate laparoscopic partial nephrectomy in a population with a hereditary predisposition to multifocal pheochromocytoma. MATERIALS AND METHODS: All patients underwent a history, physical examination, serum and urine catecholamine determinations, abdominal computerized tomography-magnetic resonance imaging and metaiodobenzylguanidine scan. The adrenal gland was exposed using a standard 3 or 4 port approach. Intraoperative ultrasound was performed using a 7.5 MHz. 10 mm. transducer placed through a 12 mm. port. After imaging the whole gland and adjacent structures partial adrenalectomy was performed based on intraoperative ultrasound images using a harmonic scalpel or alternatively using a cut and sew technique that provided a 5 mm. margin. Tumors were removed intact and sent for pathological examination. RESULTS: Since 1998, 11 patients have undergone laparoscopic partial adrenalectomy. Intraoperative ultrasound was performed in 7 patients with suspected multiple adrenal masses, including 4 and 3 who underwent unilateral and bilateral laparoscopic partial nephrectomy, respectively. Six of the 7 patients had germline defects in the von Hippel-Lindau disease gene and 1 had no identifiable alteration in the von Hippel-Lindau disease or RET gene. A solitary tumor was identified in 3 cases and multiple lesions were noted in 4. In 1 case intraoperative ultrasound localized a tumor not identified on preoperative imaging that was not readily visible via laparoscopy. Intraoperative ultrasound guided surgical dissection in all cases and identified an extra-adrenal mass in 1 patient with bilateral adrenal masses. There were no complications due to intraoperative ultrasound and no conversions to open surgery. Mean operative time was 335 minutes and mean estimated blood loss was 179 ml. Histological study demonstrated pheochromocytoma in 14 lesions and the extra-adrenal mass proved to be a splenic rest. At short-term followup no recurrences have been noted. All patients retained sufficient adrenal cortical function to avoid steroid replacement therapy. CONCLUSIONS: Laparoscopic ultrasound differentiates normal adrenal parenchyma from adrenal tumors and facilitates laparoscopic partial adrenalectomy.

Adolescent↗

Experience with 17 cases of laparoscopic adrenalectomy: use of ultrasonic aspirator and argon beam coagulator.

Between January 17, 1992 and July 31, 1993, 11 patients with primary aldosteronism, 3 with Cushing's syndrome and 3 with a nonfunctioning adrenal tumor underwent laparoscopic adrenalectomy at our university hospital. In every patient adrenal tumor was removed successfully with adjacent normal adrenal tissue. The initial 10 operations were performed without use of an ultrasonic aspirator or argon beam coagulator, and the subsequent 7 procedures were done with those items. There was no difference between the groups in intraoperative blood loss or operative time. However, the tumors in the former group were significantly smaller than those of the latter group (mean 6.70 gm. versus 13.43 gm., respectively, p < 0.05, t test). For right tumors the argon beam coagulator was useful to resect or coagulate the liver, since adrenal tumors were sometimes tightly attached to the liver and upward retraction sometimes caused liver laceration. In obese patients or those with Cushing's syndrome the ultrasonic aspirator was useful to remove retroperitoneal fat surrounding the adrenal tumor without injury to the small vessels. The mean hospital stay for these 17 patients (11.63 days) was significantly shorter than that of 16 patients with corresponding adrenal tumors undergoing open removal during the last 5 years (17.32 days, p < 0.05 t test). In conclusion, laparoscopic adrenalectomy is feasible for the surgical treatment of primary aldosteronism, Cushing's syndrome and nonfunctioning adrenal tumors. The ultrasonic aspirator and argon beam coagulator may be useful for laparoscopic adrenalectomy.

Adrenal Gland Neoplasms↗

The effects of adrenalectomy and cortisol treatment on cell types, other than corticotrophs, in the anterior pituitary of the mouse.

This investigation was designed to characterize changes due to adrenalectomy and cortisol treatment in cell types, other than corticotrophs, in the anterior pituitary of the mouse. Cortisol injections resulted in a reduced number of mammotrophs and an increased number of somatotrophs. By 5 days post-adrenalectomy an increase in the number of mammotrophs and a decrease in the number of somatotrophs was observed. No changes were noted in the number of gonadotrophs or thyrotrophs due to either adrenalectomy or cortisol treatment.

Adrenal Glands↗

Retroperitoneal laparoscopic adrenalectomy: clinical experience in 52 procedures.

OBJECTIVES: Laparoscopic adrenalectomy has become an effective option for removal of small adrenal tumors. The aim of this prospective study was to evaluate the retroperitoneal approach with regard to intraoperative complications, morbidity, and length of hospital stay. METHODS: Between September 1996 and October 1999, we performed 52 laparoscopic adrenalectomies (31 left, 21 right) for benign lesions by a retroperitoneal approach in 44 patients (27 women, 17 men) with a mean age of 46.9 years (range 17 to 74). The average adrenal tumor size was 32 mm (range 10 to 63). All procedures required four trocars and a mean operative time of 135 minutes (range 75 to 240). RESULTS: There was no mortality, conversion rate to open surgery was 1.9%, and estimated blood loss was 80 mL (range 30 to 200). With a mean follow-up of 16 months, morbidity was 17.2%, which included intraoperative complications (5. 7%) with two vascular injuries, and postoperative complications (11. 5%) with wound infections, deep hematoma, and parietal dehiscence. Average length of hospital stay was 5 days with a mean analgesic consumption of 2 days (range 1 to 5). CONCLUSIONS: The retroperitoneal approach in laparoscopic adrenalectomy appears to be a minimally invasive and safe therapeutic option that may become the standard for unilateral or bilateral adrenal tumors not larger than 7 cm. However, a learning curve in laparoscopy is indispensable before starting this type of procedure.

Adolescent↗